Cyclooctadiene derivatives

ABSTRACT

Cyclooctadiene derivative of the following formula (1): ##STR1## wherein A 1 , A 2 , A 3  and A 4  each independently represent COOR 5  (where R 5  represents a hydrogen atom, a C 1  -C 10  alkyl group, a phenyl group, a C 7  -C 12  aralkyl group or CONR 6  R 7  (where R 6  and R 7  each independently represent a hydrogen atom, a C 1  -C 10  alkyl group or a phenyl group), or A 1  and A 2 , and/or A 3  and A 4  may be combined together to represent group(s) of: ##STR2## in which X represents an oxygen atom or NR 8  {where R 8  represents a hydrogen atom, a C 1  -C 10  alkyl group or a phenyl group), 
     R 0 , R 1 , R 2 , R 3  and R 4  each independently represent a hydrogen atom, a halogen atom, a hydroxyl group and an C 1  -C 10  alkyl group, 
     the symbol ------ represents a single or double bond, and when it is a double bond, then R 1  and R 3  each independently may represent an oxygen atom; 
     provided that the case where all of R 0 , R 1 , R 2 , R 3  and R 4  represent hydrogen atoms at the same time is excluded, and agrohorticultural fungicides, antimold agents and antithrombocytic agents containing said derivatives. 
     The compounds have superior fungicidal activity, antimold activity and activity for preventing platelet aggregation, and are useful as an agrohorticultural fungicide, an antimold agent and an antithrombocytic agent.

This application is a 371 of PCT/JP95/00128 filed Feb. 1, 1995.

1. Technical Field

The present invention relates to a novel cyclooctadiene derivative, andto an agrohorticultural (agricultural and horticultural) fungicide, anantimold and an antithrombocytic agent each containing the derivative asthe active ingredient.

2. Background Art

Some cyclooctadiene derivatives have been reported in Journal of PolymerScience: Polymer Chemistry Edition, Vol. 13, p. 171 (1975), and Journalof Organic Chemistry, Vol. 42, p. 2601 (1977). However, these are usedin the field of electronic materials and as organic synthetic compounds.Nothing is referred to therein about their physiological activities suchas fungicidal activity, antimold activity and antithrombocytic activity.

Various antimolds and fungicides have heretofore been developed but areproblematic in that their effects are unsatisfactory and that some fungiwhich are resistant to them have appeared. Therefore, novel antimoldsand fungicides are desired.

In addition, since many of the fungicides that have heretofore beendeveloped are artificially-synthesized compounds, their use has becomeconsidered problematic in these days in that they have been found tohave some negative influences on the environment. For these reasons, anincreasing interest is being taken in compounds to be derived fromnatural substances, which will have few influences on the environment,and the development of fungicides comprising such compounds is thereforedesired.

On the other hand, the development of novel antithrombotic agents isalso desired for the reasons mentioned below.

It has been clarified that thrombocytoagglutination is one importantfactor in thrombogenesis in relation to its pathomorphism.Thrombogenesis is known to cause various thrombotic disorders, of whichsome typical ones include, for example, cerebral thrombosis, pulmonarythrombosis, myocardial infarction, stenocardia and peripheroarterialobstruction. It is desired to develop medicines efficacious against suchdisorders. As medicines for preventing and curing such thromboticdisorders, antithrombotic agents having an anti-thrombocytoagglutinativeactivity are specifically noted. The effect of aspirin has heretoforebeen widely studied, and recently, ticlopidine and cilostazol have beenput into clinical demonstrations. At present, however, it is stilldesired to obtain more efficacious medicines.

Apart from the above-mentioned thrombotic disorders, some otherdisorders are said to have relation to thrombocytes. Such disordersinclude, for example, nephritis and metastasis of cancer cells.Recently, a wide variety of studies are being made on the effects ofvarious antithrombotic agents having the ability to retard the functionsof thrombocytes, essentially for preventing and curing these disorders(see Journal of Royal College of Physicians, Vol. 7, No. 1, pp. 5-18,1972; Nippon Rinsyo, Vol. 4, No. 6, pp. 130-136, 1988; AnticancerResearch, Vol. 6, pp. 543-548, 1986).

DISCLOSURE OF THE INVENTION

Given the situation, the present inventors have variously studied inorder to develop excellent compounds and, as a result, have found thatcyclooctadiene derivatives to be obtained through various chemicalmodifications of Compound A that is produced by microorganisms belongingto the genus Zopfiella and also their analogs as obtained throughchemical synthesis have excellent fungicidal activity and antimoldactivity. On the basis of these findings, the inventors have completedthe present invention.

The present inventors also have found that the compounds of the presentinvention additionally have antithrombocytic activity.

Specifically, the present invention relates to a cyclooctadienederivative of the following formula (1) and also to an agrohorticulturalfungicide, an antimold and an antithrombocytic agent each comprising thederivative as the active ingredient. ##STR3## wherein A¹, A², A³ and A⁴each independently represent COOR⁵ (where R^(s) represents a hydrogenatom, a C₁ -C₁₀ alkyl group, a C₂ -C₁₀ alkenyl group, a C₂ -C₁₀ alkynylgroup, a phenyl group (the phenyl group may be optionally substituted bya halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group), or a C₇ -C₁₂ aralkylgroup (the aralkyl group may be optionally substituted by a halogenatom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxygroup, a cyano group and/or a nitro group)), or CONR⁶ R⁷ (where R⁶ andR⁷ each independently represent a hydrogen atom, a C₁ -C₁₀ alkyl groupor a phenyl group (the phenyl group may be optionally substituted by ahalogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group)), or A¹ and A², and/orA³ and A⁴ may be combined together to represent group(s) of: ##STR4## inwhich X represents an oxygen atom or NR⁸ {where R⁸ represents a hydrogenatom, a C₁ -C₁₀ alkyl group, a phenyl group (the phenyl group may beoptionally substituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or a nitrogroup), or a C₇ -C₁₂ aralkyl group (the aralkyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group)};

R⁰, R¹, R², R³ and R⁴ each independently represent a hydrogen atom, ahalogen atom, a hydroxyl group, an optionally-substituted C₁ -C₁₀ alkylgroup, an optionally-substituted C₂ -C₁₀ alkenyl group, or anoptionally-substituted C₂ -C₁₀ alkynyl group;

the substituent for the optionally-substituted groups can be any one ormore selected from the group consisting of a halogen atom, a C₁ -C₆alkyl group, a C₂ -C₆ alkenyl group, a C₂ -C₆ alkynyl group, a C₁ -C₆haloalkyl group, OR⁹ {where R⁹ represents a hydrogen atom, a C₁ -C₆alkyl group, a C₂ -C₆ alkenyl group, a C₂ -C₆ alkynyl group, a C₁ -C₆haloalkyl group, a silyl group, a C₁ -C₄ alkylsulfonyl group, a C₇ -C₁₂aralkyl group (the aralkyl group may be optionally substituted by ahalogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group), a phosphoryl group, aC₂ -C₁₀ alkoxyalkyl group, or COR¹⁴ where R¹⁴ represents a C₁ -C₆ alkylgroup, a phenyl group (the phenyl group may be optionally substituted bya halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group), a C₁ -C₆ alkoxygroup, or NR¹⁵ R¹⁶ (where R¹⁵ and R¹⁶ each independently represent ahydrogen atom, a C₁ -C₆ alkyl group or a phenyl group (the phenyl groupmay be optionally substituted by a halogen atom, a C₁ -C₆ alkyl group, aC₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or anitro group)))}, SR¹⁰ (where R¹⁰ represents a hydrogen atom, a C₁ -C₆alkyl group, a C₂ -C₆ alkenyl group, a C₂ -C₆ alkynyl group, a C₇ -C₁₂aralkyl group (the aralkyl group may be optionally substituted by ahalogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group), NR¹¹ R¹² {where R¹¹and R¹² each independently represent a hydrogen atom, a C₁ -C₆ alkylgroup, a phenyl group (the phenyl group may be optionally substituted bya halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group) or COR¹⁷ (where R¹⁷represents a C₁ -C₆ alkyl group, a phenyl group (the phenyl group may beoptionally substituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or a nitrogroup) or C₁ -C₆ alkoxy group)}, ═O, ═NR¹³ {where R¹³ represents a C₁-C₆ alkyl group, a phenyl group (the phenyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group) orOR¹⁸ (where R¹⁸ represents a hydrogen atom, a C₁ -C₆ alkyl group orCOR¹⁹ (where R¹⁹ represents a C₁ -C₆ alkyl group, a phenyl group (thephenyl group may be optionally substituted by a halogen atom, a C₁ -C₆alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, a cyanogroup and/or a nitro group) or NR²⁰ R²¹ (where R²⁰ and R²¹ eachindependently represent a hydrogen atom, a C₁ -C₆ alkyl group, a phenylgroup (the phenyl group may be optionally substituted by a halogen atom,a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, acyano group and/or a nitro group))))}, and ##STR5## (where m is aninteger of from 2 to 4); the symbol ------ represents a single or doublebond, and when it is a double bond, then R¹ and R³ each independentlymay represent an oxygen atom;

provided that the case where all of R⁰, R¹, R², R³ and R⁴ representhydrogen atoms at the same time is excluded.

The details of the substituents as referred to herein are mentionedbelow.

The halogen atom includes fluorine, chlorine, bromine and iodine atoms,but preferably fluorine, chlorine and bromine atoms.

Examples of the C₁ -C₁₀ alkyl group include methyl, ethyl, propyl,i-propyl, butyl, i-butyl, s-butyl, t-butyl, pentyl, hexyl, heptyl,octyl, nonyl and decyl groups.

Examples of the C₂ -C₁₀ alkenyl group include ethenyl, allyl, 1-butenyl,2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,2,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,2,4-hexadienyl, 1-heptenyl, 1-octenyl, 1-nonenyl and 1-decenyl groups.

Examples of the C₂ -C₁₀ alkynyl group include ethynyl, propargyl,1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl,4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl,1-heptynyl, 1-octynyl, 1-nonynyl and 1-decynyl groups.

Examples of the C₁ -C₆ alkyl group include methyl, ethyl, propyl,i-propyl, butyl, i-butyl, s-butyl, t-butyl, pentyl and hexyl groups.

Examples of the C₂ -C₆ alkenyl group include ethenyl, allyl, 1-butenyl,2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,2,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyland 2,4-hexadienyl groups.

Examples of the C₂ -C₆ alkynyl group include ethynyl, propargyl,1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl,4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl and 5-hexynylgroups.

Examples of the C₁ -C₆ haloalkyl group include fluoromethyl,difluoromethyl, trifluoromethyl, chloromethyl, bromomethyl,trifluoroethyl, trichloroethyl, trifluoropropyl, trifluorobutyl,trifluoropentyl and trifluorohexyl groups.

Examples of the C₁ -C₆ alkoxy group include methoxy, ethoxy, propoxy,i-propoxy, butoxy, i-butoxy, s-butoxy, t-butoxy, pentyloxy and hexyloxygroups.

Examples of the C₂ -C₁₀ alkoxyalkyl group include methoxymethyl,ethoxymethyl, propoxymethyl, butoxymethyl, hexyloxymethyl,octyloxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl,ethoxypropyl, propoxypropyl, methoxyethoxyethyl, ethoxyethoxymethyl,propoxyethoxymethyl, butoxyethoxymethyl, hexyloxyethoxymethyl,ethoxyethoxyethyl, butoxyethoxyethyl, hexyloxyethoxyethyl,ethoxyethoxypropyl, ethoxyethoxybutyl and tetrahydropyranyl groups.

Examples of the silyl group include trimethylsilyl andt-butyldimethylsilyl groups.

Examples of the C₁ -C₄ alkylsulfonyl group include methanesulfonyl,ethanesulfonyl, propanesulfonyl and butanesulfonyl groups.

Examples of the phosphoryl group include dimethylphosphoryl,diethylphosphoryl and diphenylphosphoryl groups.

Examples of the C₇ -C₁₂ aralkyl group include benzyl, 1-phenylethyl,2-phenylethyl, 1-phenylpropyl and 3-phenylpropyl groups.

In the formula (1), several stereoisomers and optical isomers, whichshall naturally be within the scope of the present invention, areincluded.

Preferably, R¹ represents an optionally-substituted alkyl group or anoptionally-substituted alkenyl group. The substituent, if any, in thegroup is preferably selected from a halogen atom, a C₁ -C₆ alkyl group,--OR²⁷ (where R²⁷ represents a hydrogen atom, a C₁ -C₆ alkyl group, a C₁-C₆ haloalkyl group, a silyl group, a C₁ -C₄ alkylsulfonyl group, anaralkyl group (the aralkyl group may be optionally substituted by ahalogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group), a C₂ -C₁₀ alkoxyalkylgroup or COR²⁸ (where R²⁸ represents a C₁ -C₆ alkyl group, a phenylgroup (the phenyl group may be optionally substituted by a halogen atom,a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, acyano group and/or a nitro group), C₁ -C₆ alkoxy group or NR²⁹ R³⁰(where R²⁹ and R³⁰ each independently represent a hydrogen atom, a C₁-C₆ alkyl group or a phenyl group (the phenyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group)))}, ═Oand a group of: ##STR6## (where m is an integer of from 2 to 4).

Preferably, R⁰, R² and R⁴ each independently represent a hydrogen atom,a halogen atom, a hydroxyl group or a C₁ -C₁₀ alkyl group.

Preferably, R⁴ represents a hydrogen atom, a halogen atom or a C₁ -C₁₀alkyl group.

Preferably, A¹, A², A³ and A⁴ each independently represent --COOR²²(where R²² represents a hydrogen atom or a C₁ -C₁₀ alkyl group), or A¹and A², and A³ and A⁴ are combined together to represent a group of:##STR7##

Preferably, the symbol ------ represents a single bond.

Preferred examples of the compounds of the present invention arementioned below.

(1) Cyclooctadiene derivatives of formula (1) wherein R⁰, R² and R³ eachindependently represent a hydrogen atom, a halogen atom, a hydroxylgroup or a C₁ -C₁₀ alkyl group, or R³ represents ═O.

(2) Cyclooctadiene derivatives of the above-mentioned wherein R⁴represents a hydrogen atom, a halogen atom or a C₁ -C₁₀ alkyl group.

(3) Cyclooctadiene derivatives of the above-mentioned (2) wherein A¹,A², A³ and A⁴ each independently represent COOR²² (where R²² representsa hydrogen atom or a C₁ -C₁₀ alkyl group), or A¹ and A², and A³ and A⁴are combined together to represent a group of: ##STR8##

(4) Cyclooctadiene derivatives of the above-mentioned (3), wherein R⁰,R² and R³ represent hydrogen atoms;

R⁴ represents --CH₂ CH₂ CH₂ CH₃ ;

R¹ represents a group of: ##STR9## or a group of: ##STR10## R²³represents a hydrogen atom, a halogen atom, a C₁ -C₆ alkyl group or a C₁-C₆ alkoxy group;

R²⁴ represents a hydrogen atom, a halogen atom, a C₁ -C₆ alkyl group,--OR²⁷ {where R²⁷ represents a hydrogen atom, C₁ -C₆ alkyl group, a C₁-C₆ haloalkyl group, a C₇ -C₁₂ aralkyl group (the aralkyl group may beoptionally substituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or a nitrogroup), a C₂ -C₆ alkoxyalkyl group or --COR²⁸ (where R²⁸ represents a C₁-C₆ alkyl group, a phenyl group (the phenyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group), a C₁-C₆ alkoxy group or NR²⁹ R³⁰ (where R²⁹ and R³⁰ each independentlyrepresent a hydrogen atom, a C₁ -C₆ alkyl group or a phenyl group (thephenyl group may be optionally substituted by a halogen atom, a C₁ -C₆alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, a cyanogroup and/or a nitro group)))}, or R²³ and R²⁴ are combined together torepresent ═O or a group of: ##STR11## (where m is an integer of from 2to 4); R²⁵ represents a hydrogen atom, a halogen atom or a C₁ -C₆ alkylgroup;

R²⁶ represents a hydrogen atom, a halogen atom or a C₁ -C₆ alkyl group;and

the symbol ------ represents a single or double bond.

(5) Compound of formula (2): ##STR12##

(6) Compound of formula (3): ##STR13##

(7) Compounds of formula (4): ##STR14## wherein R³¹ represents a C₁ -C₁₀alkyl group or a C₂ -C₁₀ alkenyl group.

In the present specification, "i" means "iso"; "s" means "secondary";"Me" means "methyl group"; "Et" means "ethyl group"; "Pr" means "propylgroup"; "Bu" means "butyl group", "Pen" means "pentyl group"; "Hex"means "hexyl group"; "Ph" means "phenyl group", and "Hal" means "halogenatom".

Typical examples of the compounds of formula (1) of the presentinvention are mentioned below, which, however, are not intended torestrict the scope of the present invention.

                                      TABLE 1                                     __________________________________________________________________________     ##STR15##                                                                    R.sup.1         R.sup.2    R.sup.3    R.sup.4                                 __________________________________________________________________________    Me              H          H          H                                       Et              H          H          H                                       Pr              H          H          H                                       i-Pr            H          H          H                                       Bu              H          H          H                                       i-Bu            H          H          H                                       s-Bu            H          H          H                                       Pen             H          H          H                                       Hex             H          H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          H                                       Me              H          H          Me                                      Et              H          H          Me                                      Pr              H          H          Me                                      i-Pr            H          H          Me                                      Bu              H          H          Me                                      i-Bu            H          H          Me                                      s-Bu            H          H          Me                                      Pen             H          H          Me                                      Hex             H          H          Me                                      (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          Me                                      (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          Me                                      (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          Me                                      (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          Me                                      Et              H          H          Et                                      Pr              H          H          Et                                      i-Pr            H          H          Et                                      Bu              H          H          Et                                      i-Bu            H          H          Et                                      s-Bu            H          H          Et                                      Pen             H          H          Et                                      Hex             H          H          Et                                      (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          Et                                      (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          Et                                      (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          Et                                      (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          Et                                      Pr              H          H          Pr                                      i-Pr            H          H          Pr                                      Bu              H          H          Pr                                      i-Bu            H          H          Pr                                      s-Bu            H          H          Pr                                      Pen             H          H          Pr                                      Hex             H          H          Pr                                      (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          Pr                                      (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          Pr                                      (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          Pr                                      (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          Pr                                      Bu              H          H          Bu                                      Pen             H          H          Bu                                      Hex             H          H          Bu                                      (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          Bu                                      (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          Bu                                      (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          Bu                                      (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          Bu                                      Pen             H          H          Pen                                     Hex             H          H          Pen                                     (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          Pen                                     (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          Pen                                     (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          Pen                                     (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          Pen                                     Hex             H          H          Hex                                     (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          Hex                                     (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          Hex                                     (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          Hex                                     (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          Hex                                     (CH.sub.2).sub.6 CH.sub.3                                                                     H          H          (CH.sub.2).sub.6 CH.sub.3               (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          (CH.sub.2).sub.6 CH.sub.3               (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          (CH.sub.2).sub.6 CH.sub.3               (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          (CH.sub.2).sub.6 CH.sub.3               (CH.sub.2).sub.7 CH.sub.3                                                                     H          H          (CH.sub.2).sub.7 CH.sub.3               (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          (CH.sub.2).sub.7 CH.sub.3               (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          (CH.sub.2).sub.7 CH.sub.3               (CH.sub.2).sub.8 CH.sub.3                                                                     H          H          (CH.sub.2).sub.8 CH.sub.3               (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          (CH.sub.2).sub.8 CH.sub.3               (CH.sub.2).sub.9 CH.sub.3                                                                     H          H          (CH.sub.2).sub.9 CH.sub.3               Me              Me         H          H                                       Et              Me         H          H                                       Pr              Me         H          H                                       i-Pr            Me         H          H                                       Bu              Me         H          H                                       i-Bu            Me         H          H                                       s-Bu            Me         H          H                                       Pen             Me         H          H                                       Hex             Me         H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Me         H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Me         H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Me         H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Me         H          H                                       Et              Et         H          H                                       Pr              Et         H          H                                       i-Pr            Et         H          H                                       Bu              Et         H          H                                       i-Bu            Et         H          H                                       s-Bu            Et         H          H                                       Pen             Et         H          H                                       Hex             Et         H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Et         H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Et         H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Et         H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Et         H          H                                       Pr              Pr         H          H                                       i-Pr            Pr         H          H                                       Bu              Pr         H          H                                       i-Bu            Pr         H          H                                       s-Bu            Pr         H          H                                       Pen             Pr         H          H                                       Hex             Pr         H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Pr         H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pr         H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Pr         H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pr         H          H                                       i-Pr            Bu         H          H                                       Bu              Bu         H          H                                       i-Bu            Bu         H          H                                       s-Bu            Bu         H          H                                       Pen             Bu         H          H                                       Hex             Bu         H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Bu         H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Bu         H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Bu         H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Bu         H          H                                       i-Bu            Pen        H          H                                       s-Bu            Pen        H          H                                       Pen             Pen        H          H                                       Hex             Pen        H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Pen        H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pen        H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Pen        H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pen        H          H                                       Hex             Hex        H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Hex        H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Hex        H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Hex        H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Hex        H          H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     (CH.sub.2).sub.6 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     (CH.sub.2).sub.6 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     (CH.sub.2).sub.6 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     (CH.sub.2).sub.6 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     (CH.sub.2).sub.8 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     (CH.sub.2).sub.8 CH.sub.3                                                                H          H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     (CH.sub.2).sub.9 CH.sub.3                                                                H          H                                       Me              H          Me         H                                       Et              H          Me         H                                       Pr              H          Me         H                                       i-Pr            H          Me         H                                       Bu              H          Me         H                                       i-Bu            H          Me         H                                       s-Bu            H          Me         H                                       Pen             H          Me         H                                       Hex             H          Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          Me         H                                       Et              H          Et         H                                       Pr              H          Et         H                                       i-Pr            H          Et         H                                       Bu              H          Et         H                                       i-Bu            H          Et         H                                       s-Bu            H          Et         H                                       Pen             H          Et         H                                       Hex             H          Et         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          Et         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          Et         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          Et         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          Et         H                                       Pr              H          Pr         H                                       i-Pr            H          Pr         H                                       Bu              H          Pr         H                                       i-Bu            H          Pr         H                                       s-Bu            H          Pr         H                                       Pen             H          Pr         H                                       Hex             H          Pr         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          Pr         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          Pr         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          Pr         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          Pr         H                                       i-Pr            H          Bu         H                                       Bu              H          Bu         H                                       i-Bu            H          Bu         H                                       s-Bu            H          Bu         H                                       Pen             H          Bu         H                                       Hex             H          Bu         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          Bu         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          Bu         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          Bu         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          Bu         H                                       i-Bu            H          Pen        H                                       s-Bu            H          Pen        H                                       Pen             H          Pen        H                                       Hex             H          Pen        H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          Pen        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          Pen        H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          Pen        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          Pen        H                                       Hex             H          Hex        H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          Hex        H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          Hex        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          Hex        H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     H          (CH.sub.2).sub.6 CH.sub.3                                                                H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          (CH.sub.2).sub.6 CH.sub.3                                                                H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          (CH.sub.2).sub.6 CH.sub.3                                                                H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          (CH.sub.2).sub.6 CH.sub.3                                                                H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     H          (CH.sub.2).sub.7 CH.sub.3                                                                H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          (CH.sub.2).sub.7 CH.sub.3                                                                H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          (CH.sub.2).sub.7 CH.sub.3                                                                H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     H          (CH.sub.2).sub.8 CH.sub.3                                                                H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          (CH.sub.2).sub.8 CH.sub.3                                                                H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     H          (CH.sub.2).sub.9 CH.sub.3                                                                H                                       Me              Me         Me         H                                       Et              Me         Me         H                                       Pr              Me         Me         H                                       i-Pr            Me         Me         H                                       Bu              Me         Me         H                                       i-Bu            Me         Me         H                                       s-Bu            Me         Me         H                                       Pen             Me         Me         H                                       Hex             Me         Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Me         Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Me         Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         H                                       Me              Et         Me         H                                       Et              Et         Me         H                                       Pr              Et         Me         H                                       i-Pr            Et         Me         H                                       Bu              Et         Me         H                                       i-Bu            Et         Me         H                                       s-Bu            Et         Me         H                                       Pen             Et         Me         H                                       Hex             Et         Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Et         Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Et         Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Et         Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Et         Me         H                                       Me              Pr         Me         H                                       Et              Pr         Me         H                                       Pr              Pr         Me         H                                       i-Pr            Pr         Me         H                                       Bu              Pr         Me         H                                       i-Bu            Pr         Me         H                                       s-Bu            Pr         Me         H                                       Pen             Pr         Me         H                                       Hex             Pr         Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Pr         Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pr         Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Pr         Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pr         Me         H                                       Me              Bu         Me         H                                       Et              Bu         Me         H                                       Pr              Bu         Me         H                                       i-Pr            Bu         Me         H                                       Bu              Bu         Me         H                                       i-Bu            Bu         Me         H                                       s-Bu            Bu         Me         H                                       Pen             Bu         Me         H                                       Hex             Bu         Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Bu         Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Bu         Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Bu         Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Bu         Me         H                                       Me              Pen        Me         H                                       Et              Pen        Me         H                                       Pr              Pen        Me         H                                       i-Pr            Pen        Me         H                                       Bu              Pen        Me         H                                       i-Bu            Pen        Me         H                                       s-Bu            Pen        Me         H                                       Pen             Pen        Me         H                                       Hex             Pen        Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Pen        Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pen        Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Pen        Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pen        Me         H                                       Me              Hex        Me         H                                       Et              Hex        Me         H                                       Pr              Hex        Me         H                                       i-Pr            Hex        Me         H                                       Bu              Hex        Me         H                                       i-Bu            Hex        Me         H                                       s-Bu            Hex        Me         H                                       Pen             Hex        Me         H                                       Hex             Hex        Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     Hex        Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Hex        Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     Hex        Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Hex        Me         H                                       Me              (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       Et              (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       Pr              (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       i-Pr            (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       Bu              (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       i-Bu            (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       s-Bu            (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       Pen             (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       Hex             (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                Me         H                                       Me              (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       Et              (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       Pr              (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       i-Pr            (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       Bu              (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       i-Bu            (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       s-Bu            (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       Pen             (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       Hex             (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.6 CH.sub.3                                                                     (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.8 CH.sub.3                                                                     (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     (CH.sub.2).sub.9 CH.sub.3                                                                Me         H                                       Me              Me         Et         H                                       Et              Me         Et         H                                       Pr              Me         Et         H                                       Bu              Me         Et         H                                       Pen             Me         Et         H                                       Hex             Me         Et         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Et         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Et         H                                       Me              Et         Et         H                                       Et              Et         Et         H                                       Pr              Et         Et         H                                       Bu              Et         Et         H                                       Pen             Et         Et         H                                       Hex             Et         Et         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Et         Et         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Et         Et         H                                       Me              Pr         Et         H                                       Et              Pr         Et         H                                       Pr              Pr         Et         H                                       Bu              Pr         Et         H                                       Pen             Pr         Et         H                                       Hex             Pr         Et         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pr         Et         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pr         Et         H                                       Me              Bu         Et         H                                       Et              Bu         Et         H                                       Pr              Bu         Et         H                                       Bu              Bu         Et         H                                       Pen             Bu         Et         H                                       Hex             Bu         Et         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Bu         Et         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Bu         Et         H                                       Me              Pen        Et         H                                       Et              Pen        Et         H                                       Pr              Pen        Et         H                                       Bu              Pen        Et         H                                       Pen             Pen        Et         H                                       Hex             Pen        Et         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pen        Et         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pen        Et         H                                       Me              Hex        Et         H                                       Et              Hex        Et         H                                       Pr              Hex        Et         H                                       Bu              Hex        Et         H                                       Pen             Hex        Et         H                                       Hex             Hex        Et         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Hex        Et         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Hex        Et         H                                       Me              Me         Pr         H                                       Et              Me         Pr         H                                       Pr              Me         Pr         H                                       Bu              Me         Pr         H                                       Pen             Me         Pr         H                                       Hex             Me         Pr         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Pr         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Pr         H                                       Me              Et         Pr         H                                       Et              Et         Pr         H                                       Pr              Et         Pr         H                                       Bu              Et         Pr         H                                       Pen             Et         Pr         H                                       Hex             Et         Pr         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Et         Pr         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Et         Pr         H                                       Me              Pr         Pr         H                                       Et              Pr         Pr         H                                       Pr              Pr         Pr         H                                       Bu              Pr         Pr         H                                       Pen             Pr         Pr         H                                       Hex             Pr         Pr         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pr         Pr         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pr         Pr         H                                       Me              Bu         Pr         H                                       Et              Bu         Pr         H                                       Pr              Bu         Pr         H                                       Bu              Bu         Pr         H                                       Pen             Bu         Pr         H                                       Hex             Bu         Pr         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Bu         Pr         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Bu         Pr         H                                       Me              Pen        Pr         H                                       Et              Pen        Pr         H                                       Pr              Pen        Pr         H                                       Bu              Pen        Pr         H                                       Pen             Pen        Pr         H                                       Hex             Pen        Pr         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pen        Pr         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pen        Pr         H                                       Me              Hex        Pr         H                                       Et              Hex        Pr         H                                       Pr              Hex        Pr         H                                       Bu              Hex        Pr         H                                       Pen             Hex        Pr         H                                       Hex             Hex        Pr         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Hex        Pr         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Hex        Pr         H                                       Me              Me         Bu         H                                       Et              Me         Bu         H                                       Pr              Me         Bu         H                                       Bu              Me         Bu         H                                       Pen             Me         Bu         H                                       Hex             Me         Bu         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Bu         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Bu         H                                       Me              Et         Bu         H                                       Et              Et         Bu         H                                       Pr              Et         Bu         H                                 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                   (CH.sub.2).sub.7 CH.sub.3                                                                     Pr         Bu         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pr         Bu         H                                       Me              Bu         Bu         H                                       Et              Bu         Bu         H                                       Pr              Bu         Bu         H                                       Bu              Bu         Bu         H                                       Pen             Bu         Bu         H                                       Hex             Bu         Bu         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Bu         Bu         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Bu         Bu         H                                       Me              Pen        Bu         H                                       Et              Pen        Bu         H                                       Pr              Pen        Bu         H                                       Bu              Pen        Bu         H                                       Pen             Pen        Bu         H                                       Hex             Pen        Bu         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pen        Bu         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pen        Bu         H                                       Me              Hex        Bu         H                                       Et              Hex        Bu         H                                       Pr              Hex        Bu         H                                       Bu              Hex        Bu         H                                       Pen             Hex        Bu         H                                       Hex             Hex        Bu         H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Hex        Bu         H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Hex        Bu         H                                       Me              Me         Pen        H                                       Et              Me         Pen        H                                       Pr              Me         Pen        H                                       Bu              Me         Pen        H                                       Pen             Me         Pen        H                                       Hex             Me         Pen        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Pen        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Pen        H                                       Me              Et         Pen        H                                       Et              Et         Pen        H                                       Pr              Et         Pen        H                                       Bu              Et         Pen        H                                       Pen             Et         Pen        H                                       Hex             Et         Pen        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Et         Pen        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Et         Pen        H                                       Me              Pr         Pen        H                                       Et              Pr         Pen        H                                       Pr              Pr         Pen        H                                       Bu              Pr         Pen        H                                       Pen             Pr         Pen        H                                       Hex             Pr         Pen        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pr         Pen        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pr         Pen        H                                       Me              Bu         Pen        H                                       Et              Bu         Pen        H                                       Pr              Bu         Pen        H                                       Bu              Bu         Pen        H                                       Pen             Bu         Pen        H                                       Hex             Bu         Pen        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Bu         Pen        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Bu         Pen        H                                       Me              Pen        Pen        H                                       Et              Pen        Pen        H                                       Pr              Pen        Pen        H                                       Bu              Pen        Pen        H                                       Pen             Pen        Pen        H                                       Hex             Pen        Pen        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pen        Pen        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pen        Pen        H                                       Me              Hex        Pen        H                                       Et              Hex        Pen        H                                       Pr              Hex        Pen        H                                       Bu              Hex        Pen        H                                       Pen             Hex        Pen        H                                       Hex             Hex        Pen        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Hex        Pen        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Hex        Pen        H                                       Me              Me         Hex        H                                       Et              Me         Hex        H                                       Pr              Me         Hex        H                                       Bu              Me         Hex        H                                       Pen             Me         Hex        H                                       Hex             Me         Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Hex        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Hex        H                                       Me              Et         Hex        H                                       Et              Et         Hex        H                                       Pr              Et         Hex        H                                       Bu              Et         Hex        H                                       Pen             Et         Hex        H                                       Hex             Et         Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Et         Hex        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Et         Hex        H                                       Me              Pr         Hex        H                                       Et              Pr         Hex        H                                       Pr              Pr         Hex        H                                       Bu              Pr         Hex        H                                       Pen             Pr         Hex        H                                       Hex             Pr         Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pr         Hex        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pr         Hex        H                                       Me              Bu         Hex        H                                       Et              Bu         Hex        H                                       Pr              Bu         Hex        H                                       Bu              Bu         Hex        H                                       Pen             Bu         Hex        H                                       Hex             Bu         Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Bu         Hex        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Bu         Hex        H                                       Me              Pen        Hex        H                                       Et              Pen        Hex        H                                       Pr              Pen        Hex        H                                       Bu              Pen        Hex        H                                       Pen             Pen        Hex        H                                       Hex             Pen        Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Pen        Hex        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Pen        Hex        H                                       Me              Hex        Hex        H                                       Et              Hex        Hex        H                                       Pr              Hex        Hex        H                                       Bu              Hex        Hex        H                                       Pen             Hex        Hex        H                                       Hex             Hex        Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     Hex        Hex        H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     Hex        Hex        H                                       (CH.sub.2).sub.7 CH.sub.3                                                                     (CH.sub.2).sub.7 CH.sub.3                                                                (CH.sub.2).sub.7 CH.sub.3                                                                H                                       (CH.sub.2).sub.9 CH.sub.3                                                                     (CH.sub.2).sub.9 CH.sub.3                                                                (CH.sub.2).sub.9 CH.sub.3                                                                H                                       Me              Me         Me         Me                                      Et              Me         Me         Me                                      Pr              Me         Me         Me                                      Bu              Me         Me         Me                                      Pen             Me         Me         Me                                      Hex             Me         Me         Me                                      (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         Me                                      (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         Me                                      Et              Me         Me         Et                                      Pr              Me         Me         Et                                      Bu              Me         Me         Et                                      Pen             Me         Me         Et                                      Hex             Me         Me         Et                                      (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         Et                                      (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         Et                                      Pr              Me         Me         Pr                                      Bu              Me         Me         Pr                                      Pen             Me         Me         Pr                                      Hex             Me         Me         Pr                                      (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         Pr                                      (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         Pr                                      Bu              Me         Me         Bu                                      Pen             Me         Me         Bu                                      Hex             Me         Me         Bu                                      (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         Bu                                      (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         Bu                                      Pen             Me         Me         Pen                                     Hex             Me         Me         Pen                                     (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         Pen                                     (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         Pen                                     Hex             Me         Me         Hex                                     (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         Hex                                     (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         Hex                                     (CH.sub.2).sub.7 CH.sub.3                                                                     Me         Me         (CH.sub.2).sub.7 CH.sub.3               (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         (CH.sub.2).sub.7 CH.sub.3               (CH.sub.2).sub.9 CH.sub.3                                                                     Me         Me         (CH.sub.2).sub.9 CH.sub.3               Bu              Bu         Me         Bu                                      Pen             Bu         Me         Bu                                      Hex             Bu         Me         Bu                                      Bu              Hex        Me         Bu                                      Pen             Hex        Me         Bu                                      Hex             Hex        Me         Bu                                      Bu              Bu         Bu         Bu                                      Pen             Bu         Bu         Bu                                      Hex             Bu         Bu         Bu                                      Bu              Hex        Hex        Bu                                      Pen             Hex        Hex        Bu                                      Hex             Hex        Hex        Bu                                      Bu              (CH.sub.2).sub.7 CH.sub.3                                                                (CH.sub.2).sub.7 CH.sub.3                                                                Bu                                      Pen             (CH.sub.2).sub.7 CH.sub.3                                                                (CH.sub.2).sub.7 CH.sub.3                                                                Bu                                      Hex             (CH.sub.2).sub.7 CH.sub.3                                                                (CH.sub.2).sub.7 CH.sub.3                                                                Bu                                      Bu              (CH.sub.2).sub.9 CH.sub.3                                                                (CH.sub.2).sub.9 CH.sub.3                                                                Bu                                      Pen             (CH.sub.2).sub.9 CH.sub.3                                                                (CH.sub.2).sub.9 CH.sub.3                                                                Bu                                      Hex             (CH.sub.2).sub.9 CH.sub.3                                                                (CH.sub.2).sub.9 CH.sub.3                                                                Bu                                      Pr              Cl         Cl         Pr                                      Bu              Cl         Cl         Bu                                      Pen             Cl         Cl         Pen                                     Hex             Cl         Cl         Hex                                     Pr              Br         Br         Pr                                      Bu              Br         Br         Bu                                      Pen             Br         Br         Pen                                     Hex             Br         Br         Hex                                     Pr              Cl         Pr         Cl                                      Bu              Cl         Bu         Cl                                      Pen             Cl         Pen        Cl                                      Hex             Cl         Hex        Cl                                      Pr              Br         Pr         Br                                      Bu              Br         Bu         Br                                      Pen             Br         Pen        Br                                      Hex             Br         Hex        Br                                      CH.sub.2        H          H          H                                       CHCH.sub.3      H          H          H                                       CHCH.sub.2 CH.sub.3                                                                           H          H          H                                       CH(CH.sub.2).sub.2 CH.sub.3                                                                   H          H          H                                       CH(CH.sub.2).sub.3 CH.sub.3                                                                   H          H          H                                       CH(CH.sub.2).sub.4 CH.sub.3                                                                   H          H          H                                       CH(CH.sub.2).sub.5 CH.sub.3                                                                   H          H          H                                       CH(CH.sub.2).sub.6 CH.sub.3                                                                   H          H          H                                       CH(CH.sub.2).sub.7 CH.sub.3                                                                   H          H          H                                       CH(CH.sub.2).sub.8 CH.sub.3                                                                   H          H          H                                       CHCH.sub.2      H          H          H                                       CHCHCH.sub.3    H          H          H                                       CHCHCH.sub.2 CH.sub.3                                                                         H          H          H                                       CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 H          H          H                                       CHCH(CH.sub.2).sub.3 CH.sub.3                                                                 H          H          H                                       CHCH(CH.sub.2).sub.4 CH.sub.3                                                                 H          H          H                                       CHCH(CH.sub.2).sub.5 CH.sub.3                                                                 H          H          H                                       CHCH(CH.sub.2).sub.6 CH.sub.3                                                                 H          H          H                                       CHCH(CH.sub.2).sub.7 CH.sub.3                                                                 H          H          H                                       CHCClCH.sub.2 CH.sub.3                                                                        H          H          H                                       CHCClCH.sub.2 CH.sub.2 CH.sub.3                                                               H          H          H                                       CHCMeCH.sub.2 CH.sub.3                                                                        H          H          H                                       CHCMeCH.sub.2 CH.sub.2 CH.sub.3                                                               H          H          H                                       CHCMe(CH.sub.2).sub.3 CH.sub.3                                                                H          H          H                                       CH.sub.2 CHCH.sub.2                                                                           H          H          H                                       CH.sub.2 CHCHCH.sub.3                                                                         H          H          H                                       CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                H          H          H                                       CH.sub.2 CHCHCHCH.sub.2                                                                       H          H          H                                       CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        H          H          H                                       CH.sub.2 CHCH(CH.sub.2).sub.3 CH.sub.3                                                        H          H          H                                       CH.sub.2 CHCH(CH.sub.2).sub.4 CH.sub.3                                                        H          H          H                                       CH.sub.2 CHCH(CH.sub.2).sub.5 CH.sub.3                                                        H          H          H                                       CH.sub.2 CHCH(CH.sub.2).sub.6 CH.sub.3                                                        H          H          H                                       CHCH.sub.2 CH.sub.3                                                                           H          H          Bu                                      CH(CH.sub.2).sub.2 CH.sub.3                                                                   H          H          Bu                                      CH(CH.sub.2).sub.3 CH.sub.3                                                                   H          H          Bu                                      CH(CH.sub.2).sub.4 CH.sub.3                                                                   H          H          Bu                                      CH(CH.sub.2).sub.5 CH.sub.3                                                                   H          H          Bu                                      CH(CH.sub.2).sub.6 CH.sub.3                                                                   H          H          Bu                                      CH(CH.sub.2).sub.7 CH.sub.3                                                                   H          H          Bu                                      CH(CH.sub.2).sub.8 CH.sub.3                                                                   H          H          Bu                                      CHCH.sub.2      H          H          Bu                                      CHCHCH.sub.3    H          H          Bu                                      CHCHCH.sub.2 CH.sub.3                                                                         H          H          Bu                                      CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 H          H          Bu                                      CHCH(CH.sub.2).sub.3 CH.sub.3                                                                 H          H          Bu                                      CHCH(CH.sub.2).sub.4 CH.sub.3                                                                 H          H          Bu                                      CHCH(CH.sub.2).sub.5 CH.sub.3                                                                 H          H          Bu                                      CHCH(CH.sub.2).sub.6 CH.sub.3                                                                 H          H          Bu                                      CHCH(CH.sub.2).sub.7 CH.sub.3                                                                 H          H          Bu                                      CH.sub.2 CHCH.sub.2                                                                           H          H          Bu                                      CH.sub.2 CHCHCH.sub.3                                                                         H          H          Bu                                      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                H          H          Bu                                      CH.sub.2 CHCHCHCH.sub.2                                                                       H          H          Bu                                      CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        H          H          Bu                                      CHCClCH.sub.2 CH.sub.3                                                                        H          H          Bu                                      CHCClCH.sub.2 CH.sub.2 CH.sub.3                                                               H          H          Bu                                      CHCMeCH.sub.2 CH.sub.3                                                                        H          H          Bu                                      CHCMe(CH.sub.2 CH.sub.2 CH.sub.3                                                              H          H          Bu                                      CHCMe(CH.sub.2).sub.3 CH.sub.3                                                                H          H          Bu                                      CHCH.sub.3      Bu         H          H                                       CHCH.sub.2 CH.sub.3                                                                           Bu         H          H                                       CH(CH.sub.2).sub.2 CH.sub.3                                                                   Bu         H          H                                       CH(CH.sub.2).sub.3 CH.sub.3                                                                   Bu         H          H                                       CH(CH.sub.2).sub.4 CH.sub.3                                                                   Bu         H          H                                       CHCH.sub.2      Bu         H          H                                       CHCHCH.sub.3    Bu         H          H                                       CHCHCH.sub.2 CH.sub.3                                                                         Bu         H          H                                       CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 Bu         H          H                                       CHCH(CH.sub.2).sub.3 CH.sub.3                                                                 Bu         H          H                                       CH.sub.2 CHCH.sub.2                                                                           Bu         H          H                                       CH.sub.2 CHCHCH.sub.3                                                                         Bu         H          H                                       CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                Bu         H          H                                       CH.sub.2 CHCHCHCH.sub.2                                                                       Bu         H          H                                       CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        Bu         H          H                                       CHCH.sub.3      H          Bu         H                                       CHCH.sub.2 CH.sub.3                                                                           H          Bu         H                                       CH(CH.sub.2).sub.2 CH.sub.3                                                                   H          Bu         H                                       CH(CH.sub.2).sub.3 CH.sub.3                                                                   H          Bu         H                                       CH(CH.sub.2).sub.4 CH.sub.3                                                                   H          Bu         H                                       CHCH.sub.2      H          Bu         H                                       CHCHCH.sub.3    H          Bu         H                                       CHCHCH.sub.2 CH.sub.3                                                                         H          Bu         H                                       CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 H          Bu         H                                       CHCH(CH.sub.2).sub.3 CH.sub.3                                                                 H          Bu         H                                       CH.sub.2 CHCH.sub.2                                                                           H          Bu         H                                       CH.sub.2 CHCHCH.sub.3                                                                         H          Bu         H                                       CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                H          Bu         H                                       CH.sub.2 CHCHCHCH.sub.2                                                                       H          Bu         H                                       CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        H          Bu         H                                       CHCH.sub.2      H          H          CHCH.sub.2                              CHCH.sub.2      H          CHCH.sub.2 H                                       CHCHCH.sub.3    H          H          CHCHCH.sub.3                            CHCHCH.sub.3    H          CHCHCH.sub.3                                                                             H                                       CHCHCH.sub.2 CH.sub.3                                                                         H          H          CHCHCH.sub.2 CH.sub.3                   CHCHCH.sub.2 CH.sub.3                                                                         H          CHCHCH.sub.2 CH.sub.3                                                                    H                                       CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 H          H          CHCH(CH.sub.2).sub.2 CH.sub.3           CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 H          CHCH(CH.sub.2).sub.2 CH.sub.3                                                            H                                       CH.sub.2 CHCH.sub.2                                                                           H          H          CH.sub.2 CHCH.sub.2                     CH.sub.2 CHCH.sub.2                                                                           H          CH.sub.2 CHCH.sub.2                                                                      H                                       CH.sub.2 CHCHCH.sub.3                                                                         H          H          CH.sub.2 CHCHCH.sub.3                   CH.sub.2 CHCHCH.sub.3                                                                         H          CH.sub.2 CHCHCH.sub.3                                                                    H                                       CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                H          H          CH.sub.2 CHCHCH.sub.2 CH.sub.3          CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                H          CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                           H                                       CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        H          H          CH.sub.2 CHCH(CH.sub.2).sub.2                                                 CH.sub.3                                CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        H          CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                   H                                       CH.sub.2 CHCHCHCH.sub.2                                                                       H          H          CH.sub.2 CHCHCHCH.sub.2                 CH.sub.2 CHCHCHCH.sub.2                                                                       H          CH.sub.2 CHCHCHCH.sub.2                                                                  H                                       CHCH.sub.2      CHCH.sub.2 CHCH.sub.2 CHCH.sub.2                              CHCHCH.sub.3    CHCHCH.sub.3                                                                             CHCHCH.sub.3                                                                             CHCHCH.sub.3                            CHCHCH.sub.2 CH.sub.3                                                                         CHCHCH.sub.2 CH.sub.3                                                                    CHCHCH.sub.2 CH.sub.3                                                                    CHCHCH.sub.2 CH.sub.3                   CH.sub.2 CHCH.sub.2                                                                           CH.sub.2 CHCH.sub.2                                                                      CH.sub.2 CHCH.sub.2                                                                      CH.sub.2 CHCH.sub.2                     CH.sub.2 CHCHCH.sub.3                                                                         CH.sub.2 CHCHCH.sub.3                                                                    CH.sub.2 CHCHCH.sub.3                                                                    CH.sub.2 CHCHCH.sub.3                   CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                           CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                           CH.sub.2 CHCHCH.sub.2 CH.sub.3          CH.sub.2 CHCHCHCH.sub.2                                                                       CH.sub.2 CHCHCHCH.sub.2                                                                  CH.sub.2 CHCHCHCH.sub.2                                                                  CH.sub.2 CHCHCHCH.sub.2                 C CH            H          H          H                                       C CCH.sub.3     H          H          H                                       C CCH.sub.2 CH.sub.3                                                                          H          H          H                                       C CCH.sub.2 CH.sub.2 CH.sub.3                                                                 H          H          H                                       C C(CH.sub.2).sub.3 CH.sub.3                                                                  H          H          H                                       C C(CH.sub.2).sub.4 CH.sub.3                                                                  H          H          H                                       C C(CH.sub.2).sub.5 CH.sub.3                                                                  H          H          H                                       C C(CH.sub.2).sub.6 CH.sub.3                                                                  H          H          H                                       C C(CH.sub.2).sub.7 CH.sub.3                                                                  H          H          H                                       CH.sub.2 C CH   H          H          H                                       CH.sub.2 C CCH.sub.3                                                                          H          H          H                                       CH.sub.2 C CCH.sub.2 CH.sub.3                                                                 H          H          H                                       CH.sub.2 C C(CH.sub.2).sub.2 CH.sub.3                                                         H          H          H                                       C CH            H          H          Bu                                      C CCH.sub.3     H          H          Bu                                      C CCH.sub.2 CH.sub.3                                                                          H          H          Bu                                      C CCH.sub.2 CH.sub.2 CH.sub.3                                                                 H          H          Bu                                      C C(CH.sub.2).sub.3 CH.sub.3                                                                  H          H          Bu                                      C C(CH.sub.2).sub.4 CH.sub.3                                                                  H          H          Bu                                      C C(CH.sub.2).sub.5 CH.sub.3                                                                  H          H          Bu                                      C C(CH.sub.2).sub.6 CH.sub.3                                                                  H          H          Bu                                      C C(CH.sub.2).sub.7 CH.sub.3                                                                  H          H          Bu                                      CH.sub.2 C CH   H          H          Bu                                      CH.sub.2 C CCH.sub.3                                                                          H          H          Bu                                      CH.sub.2 C CCH.sub.2 CH.sub.3                                                                 H          H          Bu                                      CH.sub.2 C C(CH.sub.2).sub.2 CH.sub.3                                                         H          H          Bu                                      C CH            Bu         H          H                                       C CCH.sub.3     Bu         H          H                                       C CCH.sub.2 CH.sub.3                                                                          Bu         H          H                                       C CCH.sub.2 CH.sub.2 CH.sub.3                                                                 Bu         H          H                                       C C(CH.sub.2).sub.3 CH.sub.3                                                                  Bu         H          H                                       C C(CH.sub.2).sub.4 CH.sub.3                                                                  Bu         H          H                                       C C(CH.sub.2).sub.5 CH.sub.3                                                                  Bu         H          H                                       C C(CH.sub.2).sub.6 CH.sub.3                                                                  Bu         H          H                                       C C(CH.sub.2).sub.7 CH.sub.3                                                                  Bu         H          H                                       CH.sub.2 C CH   Bu         H          H                                       CH.sub.2 C CCH.sub.3                                                                          Bu         H          H                                       CH.sub.2 C CCH.sub.2 CH.sub.3                                                                 Bu         H          H                                       CH.sub.2 C C(CH.sub.2).sub.2 CH.sub.3                                                         Bu         H          H                                       C CH            H          Bu         H                                       C CCH.sub.3     H          Bu         H                                       C CCH.sub.2 CH.sub.3                                                                          H          Bu         H                                       C CCH.sub.2 CH.sub.2 CH.sub.3                                                                 H          Bu         H                                       C C(CH.sub.2).sub.3 CH.sub.3                                                                  H          Bu         H                                       C C(CH.sub.2).sub.4 CH.sub.3                                                                  H          Bu         H                                       C C(CH.sub.2).sub.5 CH.sub.3                                                                  H          Bu         H                                       C C(CH.sub.2).sub.6 CH.sub.3                                                                  H          Bti        H                                       C C(CH.sub.2).sub.7 CH.sub.3                                                                  H          Bu         H                                       CH.sub.2 C CH   H          Bu         H                                       CH.sub.2 C CCH.sub.3                                                                          H          Bu         H                                       CH.sub.2 C CCH.sub.2 CH.sub.3                                                                 H          Bu         H                                       CH.sub.2 C C(CH.sub.2).sub.2 CH.sub.3                                                         H          Bu         H                                       C CH            H          H          C CH                                    C CH            H          C CH       H                                       CH.sub.2 C CH   H          H          CH.sub.2 C CH                           CH.sub.2 C CH   H          CH.sub.2 C CH                                                                            CH.sub.2 C CH                           C CH            C CH       C CH       C CH                                    CH.sub.2 C CH   CH.sub.2 C CH                                                                            CH.sub.2 C CH                                                                            CH.sub.2 C CH                           CHCHCH.sub.3    Cl         Cl         CHCHCH.sub.3                            CHCHCH.sub.3    Cl         CHCHCH.sub.3                                                                             Cl                                      CHCHCH.sub.2 CH.sub.3                                                                         Cl         Cl         CHCHCH.sub.2 CH.sub.3                   CHCHCH.sub.2 CH.sub.3                                                                         Cl         CHCHCH.sub.2 CH.sub.3                                                                    Cl                                      CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 Cl         Cl         CHCH(CH.sub.2).sub.2 CH.sub.3           CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 Cl         CHCH(CH.sub.2).sub.2 CH.sub.3                                                            Cl                                      CH.sub.2 CHCH.sub.2                                                                           Cl         Cl         CH.sub.2 CHCH.sub.2                     CH.sub.2 CHCH.sub.2                                                                           Cl         CH.sub.2 CHCH.sub.2                                                                      Cl                                      CH.sub.2 CHCHCH.sub.3                                                                         Cl         Cl         CH.sub.2 CHCHCH.sub.3                   CH.sub.2 CHCHCH.sub.3                                                                         Cl         CH.sub.2 CHCHCH.sub.3                                                                    Cl                                      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                Cl         Cl         CH.sub.2 CHCHCH.sub.2 CH.sub.3          CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                Cl         CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                           Cl                                      CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        Cl         Cl         CH.sub.2 CHCH(CH.sub.2).sub.2                                                 CH.sub.3                                CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                        Cl         CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                           Cl                                      CH.sub.2 CHCHCHCH.sub.2                                                                       Cl         Cl         CH.sub.2 CHCHCHCH.sub.2                 CH.sub.2 CHCHCHCH.sub.2                                                                       Cl         CH.sub.2 CHCHCHCH.sub.2                                                                  Cl                                      C CH            Cl         Cl         C CH                                    C CH            Cl         C CH       Cl                                      CH.sub.2 C CH   Cl         Cl         CH.sub.2 C CH                           CH.sub.2 C CH   Cl         CH.sub.2 C CH                                                                            Cl                                      CHCHCH.sub.3    Br         Br         CHCHCH.sub.3                            CHCHCH.sub.2 CH.sub.3                                                                         Br         Br         CHCHCH.sub.2 CH.sub.3                   CHCH(CH.sub.2).sub.2 CH.sub.3                                                                 Br         Br         CHCH(CH.sub.2).sub.2 CH.sub.3           CH.sub.2 CHCH.sub.2                                                                           Br         Br         CH.sub.2 CHCH.sub.2                     CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                                Br         Br         CH.sub.2 CHCHCH.sub.2 CH.sub.3          CH.sub.2 Br     H          H          H                                       CHBr(CH.sub.2).sub.3 CH.sub.3                                                                 H          H          H                                       CH.sub.2 Br     H          H          Bu                                      CHBr(CH.sub.2).sub.3 CH.sub.3                                                                 H          H          Bu                                      CH.sub.2 Cl     H          H          H                                       CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 H          H          H                                       CH.sub.2 Cl     H          H          Bu                                      CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 H          H          Bu                                      CH.sub.2 F      H          H          H                                       CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          H          H                                       CH.sub.2 F      H          H          Bu                                      CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          H          Bu                                      CHO             H          H          H                                       COCH.sub.3      H          H          H                                       CO(CH.sub.2).sub.3 CH.sub.3                                                                   H          H          H                                       CHO             H          H          Bu                                      COCH.sub.3      H          H          Bu                                      CO(CH.sub.2).sub.3 CH.sub.3                                                                   H          H          Bu                                      C(NPh)CH.sub.3  H          H          H                                       C(NPh)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          H                                       C(NPh)CH.sub.3  H          H          Bu                                      C(NPh)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          Bu                                      C(NOH)CH.sub.3  H          H          H                                       C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          H                                       C(NOH)CH.sub.3  H          H          Bu                                      C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          Bu                                      C(NOMe)CH.sub.3 H          H          H                                       C(NOMe)(CH.sub.2).sub.3 CH.sub.3                                                              H          H          H                                       C(NOMe)CH.sub.3 H          H          Bu                                      C(NOMe)(CH.sub.2).sub.3 CH.sub.3                                                              H          H          Bu                                      C(NOMe)(CH.sub.2).sub.8 CH.sub.3                                                              H          H          Bu                                      CH(OH)CH.sub.3  H          H          H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          H                                       CH(OH)CH.sub.3  H          H          Bu                                      CH(OH)CH.sub.2 CH.sub.3                                                                       H          H          Bu                                      CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                               H          H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          Bu                                      CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                               H          H          Bu                                      CH(OH)(CH.sub.2).sub.5 CH.sub.3                                                               H          H          Bu                                      CH(OH)(CH.sub.2).sub.6 CH.sub.3                                                               H          H          Bu                                      CH(OH)(CH.sub.2).sub.7 CH.sub.3                                                               H          H          Bu                                      CH(OH)(CH.sub.2).sub.8 CH.sub.3                                                               H          H          Bu                                      C(OCH.sub.3).sub.2 CH.sub.3                                                                   H          H          H                                       C(OCH.sub.3).sub.2 (CH.sub.2).sub.3 CH.sub.3                                                  H          H          H                                       C(OCH.sub.3).sub.2 CH.sub.3                                                                   H          H          Bu                                      C(OCH.sub.3).sub.2 (CH.sub.2).sub.3 CH.sub.3                                                  H          H          Bu                                      C(OCH.sub.2 CH.sub.2 O)CH.sub.3                                                               H          H          H                                       C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                              H          H          H                                       C(OCH.sub.2 CH.sub.2 O)CH.sub.3                                                               H          H          Bu                                      C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                              H          H          Bu                                      CH(OMe)CH.sub.3 H          H          H                                       CH(OMe)(CH.sub.2).sub.3 CH.sub.3                                                              H          H          H                                       CH(OMe)CH.sub.3 H          H          Bu                                      CH(OMe)(CH.sub.2).sub.3 CH.sub.3                                                              H          H          Bu                                      CH(OCH.sub.2 CHCH.sub.2)CH.sub.3                                                              H          H          H                                       CH(OCH.sub.2 CHCH.sub.2)(CH.sub.2).sub.3 CH.sub.3                                             H          H          H                                       CH(OCH.sub.2 CHCH.sub.2)CH.sub.3                                                              H          H          Bu                                      CH(OCH.sub.2 CHCH.sub.2)(CH.sub.2).sub.3 CH.sub.3                                             H          H          Bu                                      CH(OCH.sub.2 C CH)CH.sub.3                                                                    H          H          H                                       CH(OCH.sub.2 C CH)(CH.sub.2).sub.3 CH.sub.3                                                   H          H          H                                       CH(OCH.sub.2 C CH)CH.sub.3                                                                    H          H          Bu                                      CH(OCH.sub.2 C CH)(CH.sub.2).sub.3 CH.sub.3                                                   H          H          Bu                                      CH(OSiMe.sub.3)CH.sub.3                                                                       H          H          H                                       CH(OSiMe.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          H                                       CH(OSiMe.sub.3)CH.sub.3                                                                       H          H          Bu                                      CH(OSiMe.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(OSiMe.sub.3)(CH.sub.2).sub.6 CH.sub.3                                                      H          H          Bu                                      CH(OSO.sub.2 CH.sub.3)CH.sub.3                                                                H          H          H                                       CH(OSO.sub.2 CH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                               H          H          H                                       CH(OSO.sub.2 CH.sub.3)CH.sub.3                                                                H          H          Bu                                      CH(OSO.sub.2 CH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                               H          H          Bu                                      CH(OCH.sub.2 Ph)CH.sub.3                                                                      H          H          H                                       CH(OCH.sub.2 Ph)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          H                                       CH(OCH.sub.2 Ph)CH.sub.3                                                                      H          H          Bu                                      CH(OCH.sub.2 Ph)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(OPO(OMe).sub.2)CH.sub.3                                                                    H          H          H                                       CH(OPO(OMe).sub.2)(CH.sub.2).sub.3 CH.sub.3                                                   H          H          H                                       CH(OPO(OMe).sub.2)CH.sub.3                                                                    H          H          Bu                                      CH(OPO(OMe).sub.2)(CH.sub.2).sub.3 CH.sub.3                                                   H          H          Bu                                      CH(OPO(OEt).sub.2)CH.sub.3                                                                    H          H          Bu                                      CH(OPO(OEt).sub.2)(CH.sub.2).sub.3 CH.sub.3                                                   H          H          Bu                                      CH(OPO(OPh).sub.2)CH.sub.3                                                                    H          H          Bu                                      CH(OPO(OPh).sub.2)(CH.sub.2).sub.3 CH.sub.3                                                   H          H          Bu                                      CH(OCH.sub.2 OCH.sub.3)CH.sub.3                                                               H          H          H                                       CH(OCH.sub.2 OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                              H          H          H                                       CH(OCH.sub.2 OCH.sub.3)CH.sub.3                                                               H          H          Bu                                      CH(OCH.sub.2 OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                              H          H          Bu                                      CH(OTHP)CH.sub.3                                                                              H          H          H                                       CH(OTHP)(CH.sub.2).sub.3 CH.sub.3                                                             H          H          H                                       CH(OTHP)CH.sub.3                                                                              H          H          Bu                                      CH(OTHP)(CH.sub.2).sub.3 CH.sub.3                                                             H          H          Bu                                      CH(OCOCH.sub.3)CH.sub.3                                                                       H          H          H                                       CH(OCOCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          H                                       CH(OCOCH.sub.3)CH.sub.3                                                                       H          H          Bu                                      CH(OCOCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(OCOPh)CH.sub.3                                                                             H          H          Bu                                      CH(OCOPh)(CH.sub.2).sub.3 CH.sub.3                                                            H          H          Bu                                      CH(OCOPh-4-Cl)CH.sub.3                                                                        H          H          Bu                                      CH(OCOPh-2-Cl)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-3-Cl)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-4-Cl)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-2-Br)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-3-Br)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-4-Br)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-4-Me)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-4-OMe)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(OCOPh-4-CF.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                 H          H          Bu                                      CH(OCOPh-4-CN)(CH.sub.2).sub.3 CH.sub.3                                                       H          H          Bu                                      CH(OCOPh-4-NO.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                 H          H          Bu                                      CH(OCOPh-2,4-Cl.sub.2 (CH.sub.2).sub.3 CH.sub.3                                               H          H          Bu                                      CH(OCOPh-3,4-Cl.sub.2 (CH.sub.2).sub.3 CH.sub.3                                               H          H          Bu                                      CH(OCOPh-2,4-Br.sub.2)(CH.sub.2).sub.3 CH.sub.3                                               H          H          Bu                                      CH(OCOOMe)CH.sub.3                                                                            H          H          H                                       CH(OCOOMe)(CH.sub.2).sub.3 CH.sub.3                                                           H          H          H                                       CH(OCOOMe)CH.sub.3                                                                            H          H          Bu                                      CH(OCOOMe)(CH.sub.2).sub.3 CH.sub.3                                                           H          H          Bu                                      CH(OCONH.sub.2)CH.sub.3                                                                       H          H          Bu                                      CH(OCONH.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(OCONMe.sub.2)CH.sub.3                                                                      H          H          H                                       CH(OCONMe.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          H                                       CH(OCONMe.sub.2)CH.sub.3                                                                      H          H          Bu                                      CH(OCONMe.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(OCONHPh)CH.sub.3                                                                           H          H          H                                       CH(OCONHPh)(CH.sub.2).sub.3 CH.sub.3                                                          H          H          H                                       CH(OCONHPh)CH.sub.3                                                                           H          H          Bu                                      CH(OCONHPh)(CH.sub.2).sub.3 CH.sub.3                                                          H          H          Bu                                      CH(OCONHPh-4-Cl)CH.sub.3                                                                      H          H          Bu                                      CH(OCONHPh-4-Cl)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(OCONHPh-4-Br)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(OCONHPh-4-Me)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(OCONHPh-4-OMe)(CH.sub.2).sub.3 CH.sub.3                                                    H          H          Bu                                      CH(OCONHPh-4-NO.sub.2)(CH.sub.2).sub.3 CH.sub.3                                               H          H          Bu                                      CH(SH)CH.sub.3  H          H          H                                       CH(SH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          H                                       CH(SH)CH.sub.3  H          H          Bu                                      CH(SH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          Bu                                      CH(SMe)CH.sub.3 H          H          Bu                                      CH(SMe)(CH.sub.2).sub.3 CH.sub.3                                                              H          H          Bu                                      CH(SCH.sub.2 Ph)CH.sub.3                                                                      H          H          Bu                                      CH(SCH.sub.2 Ph)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(NH.sub.2)CH.sub.3                                                                          H          H          H                                       CH(NH.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                         H          H          H                                       CH(NH.sub.2)CH.sub.3                                                                          H          H          Bu                                      CH(NH.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                         H          H          Bu                                      CH(NHMe)CH.sub.3                                                                              H          H          H                                       CH(NHMe)(CH.sub.2).sub.3 CH.sub.3                                                             H          H          H                                       CH(NHMe)CH.sub.3                                                                              H          H          Bu                                      CH(NHMe)(CH.sub.2).sub.3 CH.sub.3                                                             H          H          Bu                                      CH(NMe.sub.2)CH.sub.3                                                                         H          H          Bu                                      CH(NMe.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                        H          H          Bu                                      CH(NHCOCH.sub.3)CH.sub.3                                                                      H          H          Bu                                      CH(NHCOCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(NHCOPh)CH.sub.3                                                                            H          H          Bu                                      CH(NHCOPh)(CH.sub.2).sub.3 CH.sub.3                                                           H          H          Bu                                      CH(NHCOPh-4-Cl)CH.sub.3                                                                       H          H          Bu                                      CH(NHCOPh-4-Cl)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(NHCOPh-4-Br)CH.sub.3                                                                       H          H          Bu                                      CH(NHCOPh-4-Br)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(NHCOPh-4-Me)CH.sub.3                                                                       H          H          Bu                                      CH(NHCOPh-4-Me)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(NHCOPh-4-OMe)CH.sub.3                                                                      H          H          Bu                                      CH(NHCOPh-4-OMe)(CH.sub.2).sub.3 CH.sub.3                                                     H          H          Bu                                      CH(NHCOPh-4-CN)CH.sub.3                                                                       H          H          Bu                                      CH(NHCOPh-4-CN)(CH.sub.2).sub.3 CH.sub.3                                                      H          H          Bu                                      CH(NHCOPh-4-NO.sub.2)CH.sub.3                                                                 H          H          Bu                                      CH(NHCOPh-4-NO.sub.2)(CH.sub.2).sub.3 CH.sub.3                                                H          H          Bu                                      CH(N(COPh).sub.2)CH.sub.3                                                                     H          H          Bu                                      CH(N(COPh).sub.2)(CH.sub.2).sub.3 CH.sub.3                                                    H          H          Bu                                      CH(NHCOOMe)CH.sub.3                                                                           H          H          Bu                                      CH(NHCOOMe)(CH.sub.2).sub.3 CH.sub.3                                                          H          H          Bu                                      CH(NHCOOEt)CH.sub.3                                                                           H          H          Bu                                      CH(NHCOOEt)(CH.sub.2).sub.3 CH.sub.3                                                          H          H          Bu                                      CH(NHCOOPr)CH.sub.3                                                                           H          H          Bu                                      CH(NHCOOPr)(CH.sub.2).sub.3 CH.sub.3                                                          H          H          Bu                                      COCH.sub.2 Cl   H          H          Bu                                      COCHCl(CH.sub.2).sub.2 CH.sub.3                                                               H          H          Bu                                      COCH.sub.2 Br   H          H          Bu                                      COCHBr(CH.sub.2).sub.2 CH.sub.3                                                               H          H          Bu                                      COCH.sub.2 F    H          H          Bu                                      COCHF(CH.sub.2).sub.2 CH.sub.3                                                                H          H          Bu                                      COCH.sub.2 CH.sub.3                                                                           H          H          Bu                                      COCHMe(CH.sub.2).sub.2 CH.sub.3                                                               H          H          Bu                                      COCH.sub.2 CH.sub.2 CH.sub.3                                                                  H          H          Bu                                      COCHEt(CH.sub.2).sub.2 CH.sub.3                                                               H          H          Bu                                      COCMe.sub.2 (CH.sub.2).sub.2 CH.sub.3                                                         H          H          Bu                                      CMe(OH)CH.sub.3 H          H          Bu                                      CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                              H          H          Bu                                      CEt(OH)CH.sub.3 H          H          Bu                                      CEt(OH)(CH.sub.2).sub.3 CH.sub.3                                                              H          H          Bu                                      CH(OH)-i-Pr     H          H          Bu                                      CH(OH)-i-Bu     H          H          Bu                                      CH(OH)-s-Bu     H          H          Bu                                      CHCl-i-Pr       H          H          Bu                                      CHCl-i-Bu       H          H          Bu                                      CHCl-s-Bu       H          H          Bu                                      CHBr-i-Pr       H          H          Bu                                      CHBr-i-Bu       H          H          Bu                                      CHBr-s-Bu       H          H          Bu                                      CHF-i-Pr        H          H          Bu                                      CHF-i-Bu        H          H          Bu                                      CHF-s-Bu        H          H          Bu                                      CF.sub.2 CH.sub.3                                                                             H          H          Bu                                      CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                            H          H          Bu                                      CHFCH.sub.3     H          H          CHFCH.sub.3                             CH.sub.2 CF.sub.3                                                                             H          H          CH.sub.2 CF.sub.3                       CH.sub.2 CF.sub.2 CF.sub.3                                                                    H          H          CH.sub.2 CF.sub.2 CF.sub.3              CH.sub.2 CF.sub.2 CF.sub.2 CF.sub.3                                                           H          H          CH.sub.2 CF.sub.2 CF.sub.2 CF.sub.3                                           2                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H          CH(OH)(CH.sub.2).sub.3 CH.sub.3         CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H          H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Br         H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Cl         H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Br         Br         Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Cl         Cl         Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Me         H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Et         H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Pr         H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Bu         H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Pen        H          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               Hex        H          Bu                                      CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 Cl         H          Bu                                      CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 Br         H          Bu                                      CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 Me         H          Bu                                      CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 Cl         Cl         Bu                                      CHCF(CH.sub.2).sub.3 CH.sub.3                                                                 Cl         H          Bu                                      CHCF(CH.sub.2).sub.3 CH.sub.3                                                                 Br         H          Bu                                      CHCF(CH.sub.2).sub.3 CH.sub.3                                                                 Me         H          Bu                                      CHCF(CH.sub.2).sub.3 CH.sub.3                                                                 Cl         Cl         Bu                                      CHMe(CH.sub.2).sub.3 CH.sub.3                                                                 Cl         H          Bu                                      CHMe(CH.sub.2).sub.3 CH.sub.3                                                                 Br         H          Bu                                      CHMe(CH.sub.2).sub.3 CH.sub.3                                                                 Me         H          Bu                                      Cl              H          H          H                                       Cl              Cl         H          H                                       Cl              H          Cl         H                                       Cl              Cl         Cl         H                                       Cl              Cl         Cl         Cl                                      Br              H          H          H                                       Br              Br         H          H                                       Br              H          Br         H                                       Br              Br         Br         H                                       Br              Br         Br         Br                                      I               H          H          H                                       I               I          H          H                                       I               H          I          H                                       I               I          I          H                                       I               I          I          I                                       Br              H          H          Me                                      Br              H          H          Et                                      Br              H          H          Pr                                      Br              H          H          Bu                                      Br              H          H          Pen                                     Br              H          H          Hex                                     Br              H          Me         H                                       Br              H          Et         H                                       Br              H          Pr         H                                       Br              H          Bu         H                                       Br              H          Pen        H                                       Br              H          Hex        H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH         H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          Cl         H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          Br         H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH         Me                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH         Et                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH         Pr                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH         Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH         Pen                                     CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH         Hex                                     CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          H                                       CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          Me                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          Et                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          Pr                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          Bu                                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          Pen                                     CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          Hex                                     CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O          H                                       Pen             H          O          Me                                      Pen             H          O          Et                                      Pen             H          O          Pr                                      Pen             H          O          Bu                                      Pen             H          O          Pen                                     Pen             H          O          Hex                                     CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O          H                                       CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O          Me                                      CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O          Et                                      CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O          Pr                                      CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O          Bu                                      CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O          Pen                                     CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O          Hex                                     __________________________________________________________________________

                                      TABLE 2                                     __________________________________________________________________________     ##STR16##                                                                    R.sup.1     R.sup.2                                                                              R.sup.3                                                                              R.sup.4   X.sup.1                                   __________________________________________________________________________    Me          H      H      H         H                                         Et          H      H      H         H                                         Pr          H      H      H         H                                         Bu          H      H      H         H                                         Pen         H      H      H         H                                         Hex         H      H      H         H                                         (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         H                                         (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         H                                         (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         H                                         (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         H                                         Me          H      H      H         Me                                        Et          H      H      H         Me                                        Pr          H      H      H         Me                                        Bu          H      H      H         Me                                        Pen         H      H      H         Me                                        Hex         H      H      H         Me                                        (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         Me                                        (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         Me                                        (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         Me                                        (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         Me                                        Me          H      H      H         Ph                                        Et          H      H      H         Ph                                        Pr          H      H      H         Ph                                        Bu          H      H      H         Ph                                        Pen         H      H      H         Ph                                        Hex         H      H      H         Ph                                        (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         Ph                                        (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         Ph                                        (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         Ph                                        (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         Ph                                        Me          H      H      H         Ph-4-Cl                                   Et          H      H      H         Ph-4-Cl                                   Pr          H      H      H         Ph-4-Cl                                   Bu          H      H      H         Ph-4-Cl                                   Pen         H      H      H         Ph-4-Cl                                   Hex         H      H      H         Ph-4-Cl                                   (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         Ph-4-Cl                                   (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         Ph-4-Cl                                   (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         Ph-4-Cl                                   (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         Ph-4-Cl                                   Me          H      H      H         Ph-4-Br                                   Et          H      H      H         Ph-4-Br                                   Pr          H      H      H         Ph-4-Br                                   Bu          H      H      H         Ph-4-Br                                   Pen         H      H      H         Ph-4-Br                                   Hex         H      H      H         Ph-4-Br                                   (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         Ph-4-Br                                   (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         Ph-4-Br                                   (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         Ph-4-Br                                   (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         Ph-4-Br                                   Me          H      H      H         Ph-4-Me                                   Et          H      H      H         Ph-4-Me                                   Pr          H      H      H         Ph-4-Me                                   Bu          H      H      H         Ph-4-Cl                                   Pen         H      H      H         Ph-4-Me                                   Hex         H      H      H         Ph-4-Me                                   (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         Ph-4-Me                                   (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         Ph-4-Me                                   (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         Ph-4-Me                                   (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         Ph-4-Me                                   Me          H      H      H         CH.sub.2 Ph                               Et          H      H      H         CH.sub.2 Ph                               Pr          H      H      H         CH.sub.2 Ph                               Bu          H      H      H         CH.sub.2 Ph                               Pen         H      H      H         CH.sub.2 Ph                               Hex         H      H      H         CH.sub.2 Ph                               (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         CH.sub.2 Ph                               (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         CH.sub.2 Ph                               (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         CH.sub.2 Ph                               (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         CH.sub.2 Ph                               Me          H      H      Me        H                                         Et          H      H      Me        H                                         Pr          H      H      Me        H                                         Bu          H      H      Me        H                                         Pen         H      H      Me        H                                         Hex         H      H      Me        H                                         Et          H      H      Et        H                                         Pr          H      H      Et        H                                         Bu          H      H      Et        H                                         Pen         H      H      Et        H                                         Hex         H      H      Et        H                                         Pr          H      H      Pr        H                                         Bu          H      H      Pr        H                                         Pen         H      H      Pr        H                                         Hex         H      H      Pr        H                                         Bu          H      H      Bu        H                                         Pen         H      H      Bu        H                                         Hex         H      H      Bu        H                                         Pen         H      H      Pen       H                                         Hex         H      H      Pen       H                                         Hex         H      H      Hex       H                                         Pr          Pr     H      H         H                                         Bu          Bu     H      H         H                                         Pen         Pen    H      H         H                                         Hex         Hex    H      H         H                                         Pr          Pr     H      H         Me                                        Bu          Bu     H      H         Me                                        Pen         Pen    H      H         Me                                        Hex         Hex    H      H         Me                                        Pr          H      Pr     H         H                                         Bu          H      Bu     H         H                                         Pen         H      Pen    H         H                                         Hex         H      Hex    H         H                                         Pr          H      Pr     H         Me                                        Bu          H      Bu     H         Me                                        Pen         H      Pen    H         Me                                        Hex         H      Hex    H         Me                                        Pr          H      Pr     H         Ph                                        Bu          H      Bu     H         Ph                                        Pen         H      Pen    H         Ph                                        Hex         H      Hex    H         Ph                                        CHCH.sub.2  H      H      H         H                                         CHCHCH.sub.3                                                                              H      H      H         H                                         CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         H                                         CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         H                                         CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         H                                         CH.sub.2 CHCH.sub.2                                                                       H      H      H         H                                         CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         H                                         CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         H                                         CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         H                                         CHCH.sub.2  H      H      H         Me                                        CHCHCH.sub.3                                                                              H      H      H         Me                                        CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         Me                                        CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         Me                                        CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         Me                                        CH.sub.2 CHCH.sub.2                                                                       H      H      H         Me                                        CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         Me                                        CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         Me                                        CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         Me                                        CHCH.sub.2  H      H      H         Ph                                        CHCHCH.sub.3                                                                              H      H      H         Ph                                        CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         Ph                                        CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         Ph                                        CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         Ph                                        CH.sub.2 CHCH.sub.2                                                                       H      H      H         Ph                                        CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         Ph                                        CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         Ph                                        CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         Ph                                        CHCH.sub.2  H      H      H         Ph-4-Br                                   CHCHCH.sub.3                                                                              H      H      H         Ph-4-Br                                   CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         Ph-4-Br                                   CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         Ph-4-Br                                   CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         Ph-4-Br                                   CH.sub.2 CHCH.sub.2                                                                       H      H      H         Ph-4-Br                                   CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         Ph-4-Br                                   CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         Ph-4-Br                                   CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         Ph-4-Br                                   CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     H                                         CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   H                                         CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          H                                         CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     Me                                        CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   Me                                        CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          Me                                        CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     Ph                                        CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   Ph                                        CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          Ph                                        CH.sub.2 CHCH.sub.2                                                                       CH.sub.2 CHCH.sub.2                                                                  H      H         H                                         CH.sub.2 CHCH.sub.2                                                                       H      CH.sub.2 CHCH.sub.2                                                                  H         H                                         CH.sub.2 CHCH.sub.2                                                                       CH.sub.2 CHCH.sub.2                                                                  CH.sub.2 CHCH.sub.2                                                                  CH.sub.2 CHCH.sub.2                                                                     H                                         CH.sub.2 C CH                                                                             H      H      H         H                                         CH.sub.2 C CH                                                                             H      H      CH.sub.2 C CH                                                                           H                                         CH.sub.2 C CH                                                                             CH.sub.2 C CH                                                                        H      H         H                                         CH.sub.2 C CH                                                                             H      CH.sub.2 C CH                                                                        H         H                                         CH.sub.2 C CH                                                                             CH.sub.2 C CH                                                                        CH.sub.2 C CH                                                                        CH.sub.2 C CH                                                                           H                                         CH.sub.2 C CCH.sub.3                                                                      H      H      H         H                                         CH.sub.2 C CCH.sub.3                                                                      H      H      CH.sub.2 C CCH.sub.3                                                                    H                                         CH.sub.2 C CCH.sub.3                                                                      CH.sub.2 C CCH.sub.3                                                                 H      H         H                                         CH.sub.2 C CCH.sub.3                                                                      H      CH.sub.2 C CCH.sub.3                                                                 H         H                                         CH.sub.2 C CCH.sub.3                                                                      CH.sub.2 C CCH.sub.3                                                                 CH.sub.2 C CCH.sub.3                                                                 CH.sub.2 C CCH.sub.3                                                                    H                                         CH(OH)CH.sub.3                                                                            H      H      H         H                                         CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      H         H                                         CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      H         H                                         CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      H         H                                         CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      H         H                                         CH(OH)CH.sub.3                                                                            H      H      Bu        H                                         CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        H                                         CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        H                                         CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        H                                         CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        H                                         CH(OH)CH.sub.3                                                                            H      H      Bu        Me                                        CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        Me                                        CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        Me                                        CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        Me                                        CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        Me                                        CH(OH)CH.sub.3                                                                            H      H      Bu        CH.sub.2 Ph                               CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        CH.sub.2 Ph                               CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        CH.sub.2 Ph                               CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        CH.sub.2 Ph                               CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        CH.sub.2 Ph                               CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        H                                         CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        Me                                        CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        Ph                                        CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        H                                         CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        Me                                        CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        Ph                                        CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        H                                         CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        Me                                        CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        Ph                                        CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        H                                         CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        Me                                        CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        Ph                                        C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        H                                         C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        Me                                        C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        Ph                                        C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        H                                         C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        Me                                        C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        Ph                                        CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        H                                         CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        Me                                        CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        Ph                                        CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        H                                         CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        Me                                        CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        Ph                                        CH(OCOMe)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        H                                         CH(OCOMe)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        Me                                        CH(OCOMe)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        Ph                                        CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        H                                         CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        Me                                        CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        Ph                                        CH(OH)-i-Pr H      H      Bu        H                                         CH(OH)-i-Bu H      H      Bu        H                                         CH(OH)-s-Bu H      H      Bu        H                                         CH(OH)-i-Pr H      H      Bu        Me                                        CH(OH)-i-Bu H      H      Bu        Me                                        CH(OH)-s-Bu H      H      Bu        Me                                        CH(OH)-s-Bu H      H      Bu        Ph                                        __________________________________________________________________________

                                      TABLE 3                                     __________________________________________________________________________     ##STR17##                                                                    R.sup.1     R.sup.2                                                                              R.sup.3                                                                              R.sup.4   X.sup.2                                                                              Y                                  __________________________________________________________________________    Me          H      H      H         O      H                                  Et          H      H      H         O      H                                  Pr          H      H      H         O      H                                  Bu          H      H      H         O      H                                  Pen         H      H      H         O      H                                  Hex         H      H      H         O      H                                  (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         O      H                                  (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         O      H                                  (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         O      H                                  (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         O      H                                  Me          H      H      H         O      OH                                 Et          H      H      H         O      OH                                 Pr          H      H      H         O      OH                                 Bu          H      H      H         O      OH                                 Pen         H      H      H         O      OH                                 Hex         H      H      H         O      OH                                 (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         O      OH                                 (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         O      OH                                 (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         O      OH                                 (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         O      OH                                 Me          H      H      Me        O      H                                  Et          H      H      Me        O      H                                  Pr          H      H      Me        O      H                                  Bu          H      H      Me        O      H                                  Pen         H      H      Me        O      H                                  Hex         H      H      Me        O      H                                  Et          H      H      Et        O      H                                  Pr          H      H      Et        O      H                                  Bu          H      H      Et        O      H                                  Pen         H      H      Et        O      H                                  Hex         H      H      Et        O      H                                  Pr          H      H      Pr        O      H                                  Bu          H      H      Pr        O      H                                  Pen         H      H      Pr        O      H                                  CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   O      H                                  CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          O      H                                  CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     O      OH                                 CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   O      OH                                 CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          O      OH                                 CH.sub.2 CHCH.sub.2                                                                       CH.sub.2 CHCH.sub.2                                                                  H      H         O      H                                  CH.sub.2 CHCH.sub.2                                                                       H      CH.sub.2 CHCH.sub.2                                                                  H         O      H                                  CH.sub.2 CHCH.sub.2                                                                       CH.sub.2 CHCH.sub.2                                                                  CH.sub.2 CHCH.sub.2                                                                  CH.sub.2 CHCH.sub.2                                                                     O      H                                  CH.sub.2 C CH                                                                             H      H      H         O      H                                  CH.sub.2 C CH                                                                             H      H      CH.sub.2 C CH                                                                           O      H                                  CH.sub.2 C CH                                                                             CH.sub.2 C CH                                                                        H      H         O      H                                  CH.sub.2 C CH                                                                             H      CH.sub.2 C CH                                                                        H         O      H                                  CH.sub.2 C CH                                                                             CH.sub.2 C CH                                                                        CH.sub.2 C CH                                                                        CH.sub.2 C CH                                                                           O      H                                  CH.sub.2 C CCH.sub.3                                                                      H      H      H         O      OH                                 CH.sub.2 C CCH.sub.3                                                                      H      H      CH.sub.2 C CCH.sub.3                                                                    O      OH                                 CH.sub.2 C CCH.sub.3                                                                      CH.sub.2 C CCH.sub.3                                                                 H      H         O      OH                                 CH.sub.2 C CCH.sub.3                                                                      H      CH.sub.2 C CCH.sub.3                                                                 H         O      OH                                 CH.sub.2 C CCH.sub.3                                                                      CH.sub.2 C CCH.sub.3                                                                 CH.sub.2 C CCH.sub.3                                                                 CH.sub.2 C CCH.sub.3                                                                    O      OH                                 CH(OH)CH.sub.3                                                                            H      H      H         O      H                                  CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      H         O      H                                  CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      H         O      H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      H         O      H                                  CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      H         O      H                                  CH(OH)CH.sub.3                                                                            H      H      Bu        O      H                                  CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        O      H                                  CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        O      H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        O      H                                  CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        O      H                                  CH(OH)CH.sub.3                                                                            H      H      Bu        O      OH                                 CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        O      OH                                 CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        O      OH                                 CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        O      OH                                 CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        O      OH                                 CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        O      H                                  CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        O      OH                                 CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        O      H                                  CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        O      OH                                 CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        O      H                                  CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        O      OH                                 CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        O      H                                  CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        O      OH                                 Hex         H      H      Pr        O      H                                  Bu          H      H      Bu        O      H                                  Pen         H      H      Bu        O      H                                  Hex         H      H      Bu        O      H                                  Pen         H      H      Pen       O      H                                  Hex         H      H      Pen       O      H                                  Hex         H      H      Hex       O      H                                  Pr          Pr     H      H         O      H                                  Bu          Bu     H      H         O      H                                  Pen         Pen    H      H         O      H                                  Hex         Hex    H      H         O      H                                  Pr          Pr     H      H         O      OH                                 Bu          Bu     H      H         O      OH                                 Pen         Pen    H      H         O      OH                                 Hex         Hex    H      H         O      OH                                 Pr          H      Pr     H         O      H                                  Bu          H      Bu     H         O      H                                  Pen         H      Pen    H         O      H                                  Hex         H      Hex    H         O      H                                  Pr          H      Pr     H         O      OH                                 Bu          H      Bu     H         O      OH                                 Pen         H      Pen    H         O      OH                                 Hex         H      Hex    H         O      OH                                 CHCH.sub.2  H      H      H         O      H                                  CHCHCH.sub.3                                                                              H      H      H         O      H                                  CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         O      H                                  CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         O      H                                  CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         O      H                                  CH.sub.2 CHCH.sub.2                                                                       H      H      H         O      H                                  CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         O      H                                  CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         O      H                                  CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         O      H                                  CHCH.sub.2  H      H      H         O      OH                                 CHCHCH.sub.3                                                                              H      H      H         O      OH                                 CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         O      OH                                 CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         O      OH                                 CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         O      OH                                 CH.sub.2 CHCH.sub.2                                                                       H      H      H         O      OH                                 CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         O      OH                                 CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         O      OH                                 CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         O      OH                                 CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     O      H                                  C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        O      H                                  C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        O      OH                                 C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        O      H                                  C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        O      OH                                 CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        O      H                                  CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        O      OH                                 CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        O      H                                  CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        O      OH                                 CH(OCOMC)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        O      H                                  CH(OCOMe)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        O      OH                                 CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        O      H                                  CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        O      OH                                 CH(OH)-i-Pr H      H      Bu        O      H                                  CH(OH)-i-Bu H      H      Bu        O      H                                  CH(OH)-s-Bu H      H      Bu        O      H                                  CH(OH)-s-Pen                                                                              H      H      Bu        O      H                                  CH(OH)-i-Pr H      H      Bu        O      OH                                 CH(OH)-i-Bu H      H      Bu        O      OH                                 CH(OH)-s-Bu H      H      Bu        O      OH                                 CH(OH)-s-Pen                                                                              H      H      Bu        O      OH                                 CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NH     H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NMe    H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NPh    H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NPh-4-Cl                                                                             H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NPh-4-Br                                                                             H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NPh-4-Me                                                                             H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NPh-4-OMe                                                                            H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NCH.sub.2 Ph                                                                         H                                  CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        NCH.sub.2 Ph-4-Cl                                                                    H                                  __________________________________________________________________________

                                      TABLE 4                                     __________________________________________________________________________     ##STR18##                                                                    R.sup.1     R.sup.2                                                                              R.sup.3                                                                              R.sup.4   A.sup.1                                                                            A.sup.2                                                                            A.sup.3                                                                            A.sup.4                    __________________________________________________________________________    Me          H      H      H         COOH COOH COOH COOH                       Et          H      H      H         COOH COOH COOH COOH                       Pr          H      H      H         COOH COOH COOH COOH                       Bu          H      H      H         COOH COOH COOH COOH                       Pen         H      H      H         COOH COOH COOH COOH                       Hex         H      H      H         COOH COOH COOH COOH                       (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         COOH COOH COOH COOH                       (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         COOH COOH COOH COOH                       (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         COOH COOH COOH COOH                       (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         COOH COOH COOH COOH                       Me          H      H      H         COOH COOMe                                                                              COOH COOMe                      Et          H      H      H         COOH COOMe                                                                              COOH COOMe                      Pr          H      H      H         COOH COOMe                                                                              COOH COOMe                      Bu          H      H      H         COOH COOMe                                                                              COOH COOMe                      Pen         H      H      H         COOH COOMe                                                                              COOH COOMe                      Hex         H      H      H         COOH COOMe                                                                              COOH COOMe                      (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         COOH COOMe                                                                              COOH COOMe                      (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         COOH COOMe                                                                              COOH COOMe                      (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         COOH COOMe                                                                              COOH COOMe                      (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         COOH COOMe                                                                              COOH COOMe                      Me          H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 Et          H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 Pr          H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 Bu          H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 Pen         H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 Hex         H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         COOH CONH.sub.2                                                                         COOH CONH.sub.2                 Me          H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Et          H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pr          H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Bu          H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Me          H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Et          H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Pr          H      H      H         COOEt                                                                              COOEt                                                                              CCOEt                                                                              COOEt                      Bu          H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Pen         H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Hex         H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Me          H      H      H         COOH CONHPh                                                                             COOH CONHPh                     Et          H      H      H         COOH CONHPh                                                                             COOH CONHPh                     Pr          H      H      H         COOH CONHPh                                                                             COOH CONHPh                     Bu          H      H      H         COOH CONHPh                                                                             COOH CONHPh                     Pen         H      H      H         COOH CONHPh                                                                             COOH CONHPh                     Hex         H      H      H         COOH CONHPh                                                                             COOH CONHPh                     (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         COOH CONHPh                                                                             COOH CONHPh                     (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         COOH CONHPh                                                                             COOH CONHPh                     (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         COOH CONHPh                                                                             COOH CONHPh                     (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         COOH CONHPh                                                                             COOH CONHPh                     Me          H      H      H         COOH COOPh                                                                              COOH COOPh                      Et          H      H      H         COOH COOPh                                                                              COOH COOPh                      Pr          H      H      H         COOH COOPh                                                                              COOH COOPh                      Bu          H      H      H         COOH COOPh                                                                              COOH COOPh                      Pen         H      H      H         COOH COOPh                                                                              COOH COOPh                      Hex         H      H      H         COOH COOPh                                                                              COOH COOPh                      (CH.sub.2).sub.6 CH.sub.3                                                                 H      H      H         COOH COOPh                                                                              COOH COOPh                      (CH.sub.2).sub.7 CH.sub.3                                                                 H      H      H         COOH COOPh                                                                              COOH COOPh                      (CH.sub.2).sub.8 CH.sub.3                                                                 H      H      H         COOH COOPh                                                                              COOH COOPh                      (CH.sub.2).sub.9 CH.sub.3                                                                 H      H      H         COOH COOPh                                                                              COOH COOPh                      Me          H      H      Me        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Et          H      H      Me        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pr          H      H      Me        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Bu          H      H      Me        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         H      H      Me        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      H      Me        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Et          H      H      Et        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pr          H      H      Et        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Bu          H      H      Et        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         H      H      Et        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      H      Et        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pr          H      H      Pr        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Bu          H      H      Pr        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         H      H      Pr        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      H      Pr        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Bu          H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         H      H      Pen       COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      H      Pen       COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      H      Hex       COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pr          Pr     H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Bu          Bu     H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         Pen    H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         Hex    H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pr          Pr     H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Bu          Bu     H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Pen         Pen    H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Hex         Hex    H      H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Pr          H      Pr     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Bu          H      Bu     H         COoMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pen         H      Pen    H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Hex         H      Hex    H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Pr          H      Pr     H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Bu          H      Bu     H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Pen         H      Pen    H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Hex         H      Hex    H         COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      Pr          H      Pr     H         COOPh                                                                              COOPh                                                                              COOPh                                                                              COOPh                      Bu          H      Bu     H         COOPh                                                                              COOPh                                                                              COOPh                                                                              COOPh                      Pen         H      Pen    H         COOPh                                                                              COOPh                                                                              COOPh                                                                              COOPh                      Hex         H      Hex    H         COOPh                                                                              COOPh                                                                              COOPh                                                                              COOPh                      CHCH.sub.2  H      H      H         COOH COOH COOH COOH                       CHCHCH.sub.3                                                                              H      H      H         COOH COOH COOH COOH                       CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         COOH COOH COOH COOH                       CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         COOH COOH COOH COOH                       CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         COOH COOH COOH COOH                       CH.sub.2 CHCH.sub.2                                                                       H      H      H         COOH COOH COOH COOH                       CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         COOH COOH COOH COOH                       CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         COOH COOH COOH COOH                       CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         COOH COOH COOH COOH                       CHCH.sub.2  H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHCHCH.sub.3                                                                              H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCH.sub.2                                                                       H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHCH.sub.2  H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHCHCH.sub.3                                                                              H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH.sub.2 CHCH.sub.2                                                                       H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHCH.sub.2  H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CHCHCH.sub.3                                                                              H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CHCHCH.sub.2 CH.sub.3                                                                     H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CHCH(CH.sub.2).sub.2 CH.sub.3                                                             H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CHCH(CH.sub.2).sub.3 CH.sub.3                                                             H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CH.sub.2 CHCH.sub.2                                                                       H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CH.sub.2 CHCHCH.sub.3                                                                     H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CH.sub.2 CHCH(CH.sub.2).sub.2 CH.sub.3                                                    H      H      H         CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH.sub.2 CHCH.sub.2                                                                       H      H      CH.sub.2 CHCH.sub.2                                                                     CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH.sub.2 CHCHCH.sub.3                                                                     H      H      CH.sub.2 CHCHCH.sub.3                                                                   CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                            H      H      CH.sub.2 CHCHCH.sub.2 CH.sub.3                                                          CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH.sub.2 CHCH.sub.2                                                                       CH.sub.2 CHCH.sub.2                                                                  H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCH.sub.2                                                                       H      CH.sub.2 CHCH.sub.2                                                                  H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 CHCH.sub.2                                                                       CH.sub.2 CHCH.sub.2                                                                  CH.sub.2 CHCH.sub.2                                                                  CH.sub.2 CHCH.sub.2                                                                     COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CH                                                                             H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CH                                                                             H      H      CH.sub.2 C CH                                                                           COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CH                                                                             CH.sub.2 C CH                                                                        H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CH                                                                             H      CH.sub.2 C CH                                                                        H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CH                                                                             CH.sub.2 C CH                                                                        CH.sub.2 C CH                                                                        CH.sub.2 C CH                                                                           COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CCH.sub.3                                                                      H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CCH.sub.3                                                                      H      H      CH.sub.2 C CCH.sub.3                                                                    COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CCH.sub.3                                                                      CH.sub.2 C CCH.sub.3                                                                 H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH.sub.2 C CCH.sub.3                                                                      H      CH.sub.2 C CCH.sub.3                                                                 H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)CH.sub.3                                                                            H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)CH.sub.3                                                                            H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)CH.sub.3                                                                            H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)CH.sub.3                                                                            H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OH)CH.sub.2 CH.sub.3                                                                   H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OH)(CH.sub.2).sub.2 CH.sub.3                                                           H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OH)(CH.sub.2).sub.4 CH.sub.3                                                           H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CHBr(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CHCl(CH.sub.2).sub.3 CH.sub.3                                                             H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CHF(CH.sub.2).sub.3 CH.sub.3                                                              H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CO(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      C(NOH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      C(OCH.sub.2 CH.sub.2 O)(CH.sub.2).sub.3 CH.sub.3                                          H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(CH.sub.2).sub.3 CH.sub.3                                                               H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CF.sub.2 (CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OCOMe)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OCOMe)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OCOMe)(CH.sub.2).sub.3 CH.sub.3                                                        H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CMe(OH)(CH.sub.2).sub.3 CH.sub.3                                                          H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OH)-i-Pr H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)-i-Bu H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)-s-Bu H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      CH(OH)-i-Pr H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)-i-Bu H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)-s-Bu H      H      Bu        COOEt                                                                              COOEt                                                                              COOEt                                                                              COOEt                      CH(OH)-s-Bu H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OH)-s-Pen                                                                              H      H      Bu        CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                                                                         CONH.sub.2                 CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOPh                                                                              COOPh                                                                              COOPh                                                                              COOPh                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        CONHPh                                                                             CONHPh                                                                             CONHPh                                                                             CONHPh                     CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOH COOMe                                                                              COOH COOMe                      CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOH CONH.sub.2                                                                         COOH CONH.sub.2                 CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOH CONHMe                                                                             COOH CONHMe                     CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOH CONMe.sub.2                                                                        COOH CONMe.sub.2                CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                           H      H      Bu        COOH CONHEt                                                                             COOH CONHEt                     Cl          H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Cl          Cl     H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Cl          H      Cl     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Cl          H      H      Cl        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Cl          Cl     Cl     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Cl          Cl     Cl     Cl        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          Br     H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      Br     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      Br        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          Br     Br     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          Br     Br     Br        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      I           H      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      I           I      H      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      I           H      I      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      I           H      H      I         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      I           I      I      H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      I           I      I      I         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      Me        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      Ft        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      Pr        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      Bu        COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      Pen       COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      H      Hex       COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      Me     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      Et     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      Pr     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      Bu     H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      Pen    H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      Br          H      Hex    H         COOMe                                                                              COOMe                                                                              COOMe                                                                              COOMe                      __________________________________________________________________________

                  TABLE 5                                                         ______________________________________                                         ##STR19##                                                                    R.sup.1         R.sup.2    R.sup.3                                                                              R.sup.4                                     ______________________________________                                        CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH     H                                           CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O      H                                           CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O      Me                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O      Et                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O      Pr                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O      Bu                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O      Pen                                         CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          O      Hex                                         CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH     Me                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH     Et                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH     Pr                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH     Bu                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH     Pen                                         CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          OH     Hex                                         Pen             H          O      H                                           Pen             H          O      Me                                          Pen             H          O      Et                                          Pen             H          O      Pr                                          Pen             H          O      Bu                                          Pen             H          O      Pen                                         Pen             H          O      Hex                                         CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H      H                                           CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H      Me                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H      Et                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H      Pr                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H      Bu                                          CH(OH)(CH.sub.2).sub.3 CH.sub.3                                                               H          H      Pen                                         CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O      H                                           CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O      Me                                          CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O      Et                                          CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O      Pr                                          CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O      Bu                                          CHF(CH.sub.2).sub.3 CH.sub.3                                                                  H          O      Pen                                         CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 H          O      H                                           CHBr(CH.sub.2).sub.3 CH.sub.3                                                                 H          O      H                                           CH(OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                        H          O      H                                           CH(OCH.sub.2 Ph)(CH.sub.2).sub.3 CH.sub.3                                                     H          O      H                                           CH(OCH.sub.2 OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                              H          O      H                                           CH(OTHP)(CH.sub.2).sub.3 CH.sub.3                                                             H          O      H                                           CH(OSiMe.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                      H          O      H                                           CH(OCOPh)(CH.sub.2).sub.3 CH.sub.3                                                            H          O      H                                           CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 H          O      Bu                                          CHBr(CH.sub.2).sub.3 CH.sub.3                                                                 H          O      Bu                                          CH(OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                        H          O      Bu                                          CH(OCH.sub.2 Ph)(CH.sub.2).sub.3 CH.sub.3                                                     H          O      Bu                                          CH(OCH.sub.2 OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                              H          O      Bu                                          CH(OTHP)(CH.sub.2).sub.3 CH.sub.3                                                             H          O      Bu                                          CH(OSiMe.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                      H          O      Bu                                          CH(OCOPh)(CH.sub.2).sub.3 CH.sub.3                                                            H          O      Bu                                          CHCl(CH.sub.2).sub.3 CH.sub.3                                                                 H          H      Bu                                          CHBr(CH.sub.2).sub.3 CH.sub.3                                                                 H          H      Bu                                          CH(OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                        H          H      Bu                                          CH(OCH.sub.2 Ph)(CH.sub.2).sub.3 CH.sub.3                                                     H          H      Bu                                          CH(OCH.sub.2 OCH.sub.3)(CH.sub.2).sub.3 CH.sub.3                                              H          H      Bu                                          CH(OTHP)(CH.sub.2).sub.3 CH.sub.3                                                             H          H      Bu                                          CH(OSiMe.sub.3)(CH.sub.2).sub.3 CH.sub.3                                                      H          H      Bu                                          CH(OCOPh)(CH.sub.2).sub.3 CH.sub.3                                                            H          H      Bu                                          ______________________________________                                    

Methods for producing the compounds of the present invention arementioned below.

Production Method 1

A method is disclosed in Japanese Patent Application Laid-open No.6-184157, U.S. Pat. No. 5,346,919 and European Patent ApplicationLaid-open No. 582,267, comprising incubating microorganisms of a strainbelonging to the genus Zopfiella, preferably those of Zopfiella curvatato produce Compound A (Zopfiellin) of the following structural formula(A) in the culture followed by isolating the product from the culturethrough various means of concentration under reduced pressure,freeze-drying, extraction with an organic solvent such as methanol,ethanol, propanol, butanol, acetone, ethyl acetate, chloroform orbenzene, chromatography with an adsorbent such as an ion-exchange resin,a non-ionic adsorbing resin, active charcoal, silica gel or alumina,gelfiltration and crystallization, which can be employed singly or incombination or repetition thereof in any desired order. ##STR20##

Starting from Compound A, the compounds of the present invention can beobtained by various chemical reactions of the Compound A.

1. Conversion of acid anhydride moiety

1-(1). Carboxylic acids, esters, amides and imido compounds

Compound A can be hydrolyzed under acidic conditions (for example, inthe presence of hydrochloric acid or sulfuric acid) or alkalineconditions (for example, in the presence of sodium hydroxide orpotassium hydroxide) to produce carboxylic acid derivatives.

The resulting carboxylic acid derivative can be reacted with any ofalcohols such as methanol and ethanol, or amines such as ammonia,methylamine, dimethylamine and aniline, in the presence of a condensingagent such as DCC to produce ester derivatives and amide derivatives.When Compound A is reacted with any of such alcohols or aminesoptionally in the presence of a base such as potassium carbonate ort-BuOK as added thereto, then partial esters, amides and imidoderivatives can be produced. ##STR21##

In these formulae, R⁵, R⁶ and R⁷ have the same meanings as definedabove.

1-(2). Lactone derivatives

Compound A can be reduced with a reducing agent, such as lithiumaluminium hydride (LiAlH₄), to produce lactone derivatives. ##STR22## 2.Conversion of chain-structured moiety 2-(1). Halide compounds

The hydroxyl group in Compound A and its equivalent analogs (these meanmodifications to be derived from Compound A by converting its acidanhydride moiety into dicarboxylic acids, esters, amides and imides) canbe converted into a halide by means of conventional methods forconverting a hydroxyl group into a halide.

The reactants to be employed herein includes, for example, afluorinating agent such as diethylaminosulfur trifluoride (DAST), achlorinating agent such as thionyl chloride (SOCl₂) or carbontetrachloride-triphenylphosphine (CCl₄ --PPh₃), and a brominating agentsuch as bromine-triphenylphosphine (Br₂ --PPh₃). ##STR23##

In these formulae, A¹, A² , A³ and A⁴ have the same meanings as definedabove; and Hal represents a halogen atom.

2-(2). Sulfonylation of hydroxyl group

Compound A and its equivalent analogs can be reacted with asulfonylating agent such as methanesulfonyl chloride (CH₃ SO₂ Cl) orethanesulfonyl chloride (C₂ H₅ SO₂ Cl) optionally in the presence of abase such as triethylamine (Et₃ N), pyridine or potassium carbonate asadded thereto to produce sulfonylated derivatives. ##STR24##

In these formulae, A¹, A², A³ and A⁴ have the same meanings as definedabove, and R³² represents a C₁ -C₄ alkyl group.

2-(3). Acylation, carbamoylation and alkoxycarbonylation of hydroxylgroup

Compound A and its equivalent analogs can be reacted with acid halidessuch as acetyl chloride (CH₃ COCl) or benzoyl chloride (PhCOCl), or acidanhydrides such as acetic anhydride, optionally in the presence of abase such as triethylamine (Et₃ N), pyridine or potassium carbonate asadded thereto to produce acylated derivatives.

Compound A and its equivalent analogs can be reacted with isocyanatessuch as methyl isocyanate (CH₃ NCO) or phenyl isocyanate (PhNCO), orcarbamoyl halides such as dimethylaminocarbamoyl chloride ((CH₃)₂NCOCl), optionally in the presence of a base such as triethylamine (Et₃N), pyridine or potassium carbonate as added thereto producecarbamoylated derivatives.

Compound A and its equivalent analogs can be reacted with alkoxycarbonylhalides such as methyl chloroformate (ClCOOCH₃) or ethyl chloroformate(ClCOOC₂ H₅), optionally in the presence of a base such as triethylamine(Et₃ N), pyridine or potassium carbonate as added thereto to producealkoxycarbonylated derivatives. ##STR25##

In these formulae, A¹, A², A³, A⁴ and R¹⁰ have the same meanings asdefined above.

2-(4). Alkylation, alkenylation, alkynylation and aralkylation ofhydroxyl group

Compound A and its equivalent analogs can be reacted with an alkylatingagent such as methyl iodide (CH₃ I), ethyl iodide (C₂ H₅ I) ordimethylsulfate ((CH₃)₂ SO₄), an alkenylating agent such as allylbromide (CH₂ ═CHCH₂ Br), an alkynylating agent such as propargylchloride (CH.tbd.CCH₂ Cl), or an aralkylating agent such as benzylchloride (PhCH₂ Cl) or β-phenylethyl chloride (PhCH₂ CH₂ Cl) to producealkylated, alkenylated, alkynylated or aralkylated derivatives.##STR26##

In these formulae, A¹, A², A³, A⁴ and R⁹ have the same meanings asdefined above.

2-(5). Thiolation of hydroxyl group

The compounds as obtained in 2-(1) or 2-(2) can be reacted with ahydrosulfiding agent such as sodium hydrosulfide (NaSH). The resultingderivatives can be processed in the same manner as in 2-(4) to producevarious sulfur-containing derivatives. ##STR27##

In these formulae, A¹, A², A³, A⁴ and R¹³ have the same meanings asdefined above.

2-(6). Silylation, phosphorylation and alkoxyalkylation of hydroxylgroup

Compound A and its equivalent analogs can be reacted with silylatedcompounds such as trimethylsilyl chloride ((CH₃)₃ SiCl),t-butyldimethylsilyl chloride ((t-Bu(CH₃)₂ SiCl), optionally in thepresence of a base such as triethylamine (Et₃ N), pyridine or potassiumcarbonate to produce silylated derivatives.

Compound A and its equivalent analogs can be reacted with phosphoricesters such as diethylphosphoryl chloride ((EtO)₂ POCl) ordiphenylphosphoryl chloride ((PhO)₂ POCl), optionally in the presence ofa base such as triethylamine (Et₃ N), pyridine or potassium carbonate toproduce phosphorylated derivatives.

Compound A and its equivalent analogs can be reacted with alkoxyalkylhalides such as methoxymethyl chloride (CH₃ OCH₂ Cl) or ethoxyethylchloride (C₂ H₅ OCH₂ CH₂ Cl) optionally in the presence of a base suchas potassium carbonate or sodium hydroxide, or with compounds such asdihydropyran in the presence of an acid catalyst such asp-toluenesulfonic acid (p-TsOH) as added thereto, to producealkoxyalkylated derivatives. ##STR28##

In these formulae, A¹, A², A³, A⁴ and R⁹ have the same meanings asdefined above.

2-(7). Oxidation of hydroxyl group

Compound A and its equivalent analogs can be oxidized with any ordinaryoxidizing agent to produce carbonyl derivatives. Any and every ordinaryoxidizing agent capable of oxidizing a secondary hydroxyl group into acarbonyl group can be used. Generally employed herein is oxidation withan inorganic oxidizing agent such as chromic acid and permanganates, anorganic oxidizing agent such as DMSO, or oxygen. ##STR29##

In these formulae, A¹, A², A³ and A⁴ have the same meanings as definedabove.

2-(8). Ketal compounds

The carbonyl compounds as obtained in 2-(7) can be reacted with alcoholssuch as ethylene glycol, in the presence of an acid catalyst such asp-toluenesulfonic acid (p-TsOH) to produce ketal derivatives. ##STR30##

In these formulae, A¹, A², A³, A⁴ and m have the same meanings asdefined above.

2-(9). Oximes, imino compounds

The carbonyl compounds as obtained in 2-(7) can be reacted with aminessuch as methylamine (CH₃ NH₂) or aniline (PhNH2) under de-wateringconditions to produce iminated derivatives. If they are reacted withhydroxyamines under de-watering conditions, oximated derivatives can beproduced.

To carry out the reaction under de-watering conditions, the compoundsare reacted in an alcohol or in the presence of a molecular sieve in aninert solvent.

The oximes obtained herein can be further processed in the same manneras in the above-mentioned 1-(2) to 1-(4) to produce differently-modifiedoxime derivatives. ##STR31##

In these formulae, A¹, A², A³, A⁴ and R¹⁷ have the same meanings asdefined above.

2-(10). Aminated compounds

The compounds as obtained in 2-(1) or 2-(2) can be reacted with aminesto produce aminated derivatives.

The amines include, for example, methylamine and dimethylamine.

The oximes obtained in 2-(9) can be reduced through hydrogenation, forexample, with a Raney nickel or the like catalyst to produce aminederivatives.

The derivatives obtained herein can be processed in the same manner asin 2-(3) to produce differently-modified amine derivatives. ##STR32##

In these formulae, A¹, A², A³, A⁴, R¹⁴, R¹⁵ and Hal have the samemeanings as defined above.

2-(11). Hydrogenation of hydroxyl group

The compounds as obtained in 2-(1) can be reduced with a reducing agentsuch as tributyl tin hydride (nBu₃ SnH) to produce hydrogenatedderivatives. ##STR33##

In these formulae, A¹, A², A³, A⁴ and Hal have the same meanings asdefined above.

2-(12). Introduction of double bond

The compounds as obtained in 2-(1) or 2-(2) can be reacted with a basesuch as DBN, DBU or t-BuOK to thereby introduce a double bond into thecompounds through the removal of HHal therefrom. The position into whichthe double bond is introduced varies, depending on the base used, thetype of the solvent used and the reaction temperature. The compoundsthus having the double bond as introduced thereinto can be isomerizedthrough reaction with a base.

In these formulae, A¹, A², A³, A⁴ and Hal have the same meanings asdefined above. ##STR34## 2-(13). Conversion of carbon chain--Part (1)

The compounds as obtained in 2-(12) can be oxidized, for example,through ozonation and then treated with DMS or the like to producecarbonyl derivatives from which the carbon chain has been cleaved at thedouble bond moiety. The carbonyl compounds obtained herein can bereduced with a reducing agent such as sodium borohydride (NaBH₄) wherebythe carbonyl group is converted into a hydroxyl group. The hydroxylgroup in the resulting compounds can be modified in the same manner asmentioned hereinabove to give differently-modified derivatives.##STR35##

In these formulae, A¹, A², A³ and A⁴ have the same meanings as definedabove.

2-(14). Conversion of carbon chain--Part (2)

The compounds as obtained in 2-(13) can be reacted with an alkyl lithium(RLi) or a Grignard reagent (R--MgHal), or through Reformatsky reaction(with R--Zn--Hal) to thereby introduce different carbon chains into thecompounds. The hydroxyl group as produced in the resulting compoundsthrough the reaction can be modified in the same manner as mentionedhereinabove to give differently-modified derivatives. ##STR36##

In these formulae, A¹, A², A³ and A⁴ have the same meanings as definedabove; and R has the same meaning as R¹.

2-(15). Conversion of carbon chain--Part (3)

The compounds as obtained in 2-(7) can be reacted with R-L (wherein Lrepresents a removable group such as a halogen atom; and R represents analkyl group, an alkenyl group, an alkynyl group or a haloalkyl group) inthe presence of a base such as sodium hydride (NaH) or t-BuOK to therebyintroduce different carbon chains into the compounds. ##STR37##

In these formulae, A¹, A², A³ and A⁴ have the same meanings as definedabove.

2-(16). Introduction of oxygen atom--Part (1)

The compounds as obtained in 2-(7) can be reacted with peroxides, suchas hydrogen peroxide or m-chloro-perbenzoic acid (mCPBA), throughBayer-Villiger reaction to thereby introduce an oxygen atom into thecompounds. The resulting compounds can be hydrolyzed to therebyintroduce a hydroxyl group thereinto. ##STR38##

In these formulae, A¹, A², A³ and A⁴ have the same meanings as mentionedabove.

2-(17). Introduction of oxygen atom--Part (2)

The compounds as obtained in 2-(12) can be reacted with peroxides, suchas hydrogen peroxide or m-chloro-perbenzoic acid (mCPBA), to produceepoxy compounds. The resulting compounds can be reacted alkyl lithium(RLi) compounds such as methyl lithium, or with alkoxide compounds suchas sodium methoxide, to thereby introduce an alkyl or alkoxy group intothe compounds. The hydroxyl group as produced in the resulting compoundsthrough the reaction can be modified in the same manner as mentionedhereinabove to give differently-modified derivatives. ##STR39##

In these formulae, A¹, A², A³ and A⁴ have the same meanings as definedabove; and R has the same meaning as R¹.

In addition to the methods mentioned hereinabove, any other ordinarymethods capable of being employed in organic synthesis can be naturallyemployed for differently modifying compound A.

The above-mentioned production methods can be conducted in suitableinert solvents. The solvents employable in these include hydrocarbonssuch as toluene and xylene; halogenated hydrocarbons such aschlorobenzene and dichloroethane; ethers such as tetrahydrofuran,diisopropyl ether and dioxane; esters such as ethyl acetate; nitrilessuch as acetonitrile; alcohols such as methyl alcohol and ethyl alcohol;and polar solvents such as dimethylsulfoxide and dimethylformamide.

The reaction temperatures can be freely settled but, in general, shouldpreferably fall between -70° C. and 200° C. or the reflux temperaturefor the solvent used.

Next, full-synthetic methods for producing the compounds of the presentinvention are mentioned below.

Production Method 2

A method for producing cyclooctadiene, such as that mentioned below, hasbeen reported in Journal of Chemical Society (B), pp. 1552-1564, 1971;and Journal of Polymer Science: Polymer Chemistry Edition, Vol. 13, pp.171-187, 1975. ##STR40##

Another method for producing cyclooctadienes, such as that mentionedbelow, has been reported in Journal of Organic Chemistry, Vol. 42, pp.2601-2610, 1977. ##STR41## wherein X has the same meaning as definedabove.

It is possible to react these cyclooctadienes with a halogenating agent,such as chlorine molecule, bromine molecule or N-bromosuccinimide (NBS),thereby introducing a halogen atom thereinto. ##STR42## wherein A¹, A²,A³, A⁴ and Hal have the same meanings as defined above; R has the samemeaning as R¹ ; and n is an integer of from 1 to 4.

The halogen atom thus introduced into these compounds can be convertedinto other different substituents in accordance with the methodsmentioned hereinabove or with any other ordinary means.

Production Method 3

A process for producing cyclooctadiene, such as that mentioned below,has been reported in Journal of Organic Chemistry, Vol. 58, pp.2377-2380, 1993. ##STR43##

The product as obtained according to this process can be oxidized withan ordinary oxidizing agent to give the following: ##STR44## Anyordinary oxidizing agent capable of oxidizing a primary alcohol into acarboxylic acid can be employed for the oxidation. In general,employable are inorganic oxidizing agents such as potassium permanganateand chromic acid and also oxidation with oxygen in the presence of acatalyst such as platinum. The dicarboxylic acid or acid anhydridemoiety in the resulting compounds can be converted, for example,according to the methods mentioned hereinabove, into esters, amides andlactones.

Next, the reaction on the double bond moiety in these compounds isreferred to hereinunder.

3-(1). Halogen addition ##STR45## wherein A¹, A², A³, A⁴ and Hal havethe same meanings as defined above; R has the same meaning as R¹.

Halogen molecules, such as bromine, can be added to the compounds asobtained in the above, whereby halogen atoms can be introducedthereinto. The resulting halogenated compounds can be processed in thesame manner as mentioned hereinabove to thereby introduce differentsubstituents, such as an alkyl group, into the compounds. ##STR46##wherein A¹, A², A³ and A⁴ and Hal have the same meanings as definedabove; and R has the same meaning as R¹.

The compounds as obtained in the above can be reacted with peroxidessuch as hydrogen peroxide or m-chloroperbenzoic acid (mCPBA) to produceepoxy compounds. The resulting epoxy compounds can be reacted with alkyllithium compounds (RLi) such as methyl lithium, to thereby introduce analkyl group thereinto. The hydroxyl group as produced in the resultingcompounds can be modified, according to various methods such as thosementioned hereinabove, into different substituents.

In addition to the methods of 3-(1) and 3-(2), it is naturally possibleto modify the double bond in the compounds according to any ordinarymethods generally employed in organic synthesis to givedifferently-modified derivatives.

Production Method 4

A method for producing 9-membered cyclic compounds (nonanolides) hasbeen reported in Journal of the American Chemical Society, Vol. 94, pp.4735-4737, 1972.

Referring to this method, one can produce the compounds of the presentinvention according to the following reaction route. ##STR47## whereinR¹, R², R³ and R⁴ have the same meanings as defined above.

Briefly, intermediates 1 and 2 are reacted in the presence of a basesuch as sodium hydride (NaH) or t-BuOK, to give an intermediate 3. Theintermediate 3 is reacted with hydroxylamine to give an oximederivative, which may then be subjected to rearrangement, for example,through reaction with phosphorus oxychloride or the like to therebyconstruct a 8-membered ring structure (intermediate 4).

The cyano group of the intermediate 4 is removed, for example, throughhydrolysis and decarboxylation, or is reacted with an alkyl lithium(R--Li) or the like to thereby introduce an alkyl group into theintermediate 4, and thereafter the double bond is reduced, for example,through hydrogenation to produce a compound 5.

The compound 5 is then reacted with BBr₃ to remove the tetramethyl ethermoiety therefrom, thereby giving a hydroquinone derivative, which isthereafter oxidized with potassium permanganate or the like and thenreacted with lead tetraacetate or the like to produce the intendedproduct. The product can also be produced through oxidation withozonation.

Starting from an intermediate 3', it is also possible to obtain thecompounds of the present invention in accordance with the followingreaction route. ##STR48##

Briefly, an intermediate 3' is reacted with a peroxide, such as hydrogenperoxide or m-chloro-perbenzoic acid (m-CPBA) through Bayer-Villigerreaction to give a lactone derivative 6, which is then reacted with aGrignard reagent or an alkyl lithium reagent to give a compound 7. Next,the compound 7 is reacted with a reducing agent such as lithiumaluminium hydride (LiAlH₄) to produce a compound 8. The compound 8 isoxidized and then reacted with R⁴ --Hal in the presence of a base suchas sodium hydride to give a compound 9. The carbonyl group of theresulting intermediate 9 is processed through Wittig reaction or thelike to thereby introduce a carbon chain into the compound, or istreated with a reducing agent such as a Raney nickel to obtain acompound 10. Then, the compound 10 is processed in the same manner asabove to produce the intended product.

Production Method 5

Another method for producing 9-membered cyclic compounds (nonanolides)has been reported in Journal of the American Chemical Society, Vol. 114,pp. 9673-9674, 1992.

Referring to this method, one can produce the compounds of the presentinvention according to the following reaction route. ##STR49## whereinR¹, R², R³ and R⁴ have the same meanings as defined above.

Briefly, intermediates 11 and 12 are reacted in the presence of acondensing agent such as DCC to give an intermediate 13. Theintermediate 13 is subjected to photoreaction and then heated to give acompound 14. The lactone moiety in the compound 14 is hydrolyzed andthen oxidized with potassium permanganate or the like to obtain theintended product.

The compounds of the present invention which can be produced inaccordance with these production methods 1 to 5 encompass severalstereoisomers and optical isomers, which shall naturally be within thescope of the present invention.

The compounds of the present invention thus Produced in the manner asmentioned hereinabove are active against various types of mold and aretherefore useful as antimolds in medical use, antimolds for animals,fungicides in agricultural use, antimolds for foods, antimolds inindustrial use, and even in antithrombocytic agents.

Concretely, the compounds of the present invention are active againstvarious phytopathogenic fungi that will do serious harm in agriculture,such as Damping-off, Pythium (Pythium debaryanum), Late blight(Phytophthora infestans), Sclerotinia rot (Sclerotinia sclerotiorum),Brown rot (Sclerotinia cinerea), Scab (Venturia inaequalis), Glumeblotch (Septoria nodorum), Melanose (Diaporthe citra). Net blotch(Pyrenophora teres), Gray mold (Botrytis cinerea), Blast (Pyriculariaoryzae), Anthracnose (Colletotrichum lagenarium), Eyespot(Pseudocercosporella herpotrichoides), Leaf blotch (Rhynchosporiumsecalis), Alternaria leaf spot (Alternaria mali), Fusarium wilt(Fusarium oxysporum), Sheath blight (Rhizoctonia solani) andDamping-off, Rhizoctonia (Rhizoctonia solani); and also against variousmicroorganisms that will do serious harm in medicine and industry, suchas Aspergillus nigar, Aspergillus fumigatus, Trichophytonmentagrophytes, Trichophyton rubrum, Penicillium citrinum, Candidaalbicans and Saccharomyces cerevisiae.

In addition, as exhibiting an anti-thrombocytoagglutinative activity,the compounds of the present invention can be used in antithrombocyticagents for curing and preventing various thrombotic disorders, such ascerebral thrombosis, pulmonary thrombosis, myocardial infarction,stenocardia and peripheroarterial obstruction.

Where the compounds of the present invention are used inagrohorticultural fungicides, any carriers that do not detract from theactivity of the compounds can be used. Generally usable are solidcarriers, such as clay, talc, bentonitc and diatomaceous earth, whichcan be combined with any of suitable liquid carriers, such as water,alcohols (e.g., methanol, ethanol), aromatic hydrocarbons benzene,toluene, xylene), chlorinated hydrocarbons, ethers, ketones, esters(e.g., ethyl acetate) and acid amides (e.g., dimethylformamide). Ifdesired, any of emulsifiers, dispersing agents, suspending agents,penetrants, excipients and stabilizers can be added to the compoundsalong with the carriers and formulated into any preparations of liquidsolutions, oil solutions, emulsifiable concentrates, wettable powders,dusts, granules and flowables for practical use.

The dose of the preparation comprising the compound of the presentinvention varies, depending on the site to which it is applied, the timewhen it is applied, the method how it is applied, the disease againstwhich it is applied and the crop for which it is applied, but may begenerally from 5 g/ha to 50 kg/ha in terms of the active ingredient orthe compound of the invention in the preparation.

If desired, the preparation may be combined with any of variousherbicides, fungicides, insecticides, plant growth regulating agents,agonists and fertilizers, while it is formulated or sprayed.

On the other hand, where the compounds of the present invention are usedin antimolds in medical use, for example, they can be formulated intoliquid liniments, gels or ointments, which can be applied to theaffected parts to cure them.

Where the compounds of the present invention are used inantithrombocytic agents, the agents can be formulated for parenteraladministration, for example, into injections (for intravenous,intramuscular and intraabdominal administration), ointments,suppositories and aerosols, or for peroral administration, for example,into tablets, capsules, granules, pills, syrups, liquid preparations,emulsions and suspensions.

The above-mentioned pharmaceutical compositions comprising the compoundof the present invention contains the compound in an amount ofapproximately from 0.1 to 99.5% by weight, preferably approximately from0.5 to 95% by weight, relative to the total weight of the composition.

The compounds of the present invention and the pharmaceuticalcompositions comprising the compound may additionally contain any otherpharmaceutically-active compounds. The pharmaceutical composition maycontain a plurality of the compounds of the invention as combined.

The clinical dose of the compound of the present invention varies,depending on the age, the body weight, the sensitivity and the conditionof the patient to which it applied, but the effective dose thereof shallbe from 0.003 to 1.5 g/day/adult or so, preferably from 0.01 to 0.6g/day/adult or so. If desired, however, any dose overstepping theabove-mentioned range is also applicable.

The compounds of the present invention can be formulated intopharmaceutical preparations for clinical administration according toconventional means.

For example, they can be formulated into tablets, capsules, granules andpills for peroral administration along with vehicles such as whitesugar, lactose, glucose, starch and mannitol; binders such ashydroxypropyl cellulose, syrup, arabic gum, gelatin, sorbitol,tragacanth, methyl cellulose and polyvinyl pyrrolidone; disintegratorssuch as starch, carboxymethyl cellulose and its calcium salt,microcrystalline cellulose and polyethylene glycol; and lubricants suchas talc, magnesium or calcium stearate, silica, sodium laurate andglycerol.

They can also be formulated into injections, liquid preparations,emulsifiable concentrates, suspensions, syrups and aerosols along withsolvents for the active ingredient, such as water, ethyl alcohol,isopropyl alcohol, propylene glycol, 1,3-butylene glycol andpolyethylene glycol, surfactants such as sorbitan fatty acid esters,polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acidesters, polyoxyethylene ether of hydrogenated castor oil and lecithin;suspending agents such as cellulose derivatives (e.g., sodiumcarboxymethyl cellulose, methyl cellulose) and natural rubbers (e.g.,tragacanth, arabic gum); preservatives such as paraoxybenzoates,benzalkonium chloride and sorbates.

To formulate endermic ointments comprising the compound of the presentinvention, for example, employable are white petrolatum, liquidparaffin, higher alcohols, Macrogol ointment bases, hydrophilic ointmentbases and aqueous gel bases.

Suppositories comprising the compound of the present invention can beformulated along with cacao butter, polyethylene glycol, lanolin, fattyacid triglycerides, coconut oil and polysorbates.

BEST MODES OF CARRYING OUT THE INVENTION

The present invention is described in more detail by means of thefollowing examples, which, however, are not whatsoever intended torestrict the scope of the invention.

Reference Example 1

Zopfiella curvata No. 37-3 strain was cultured at 25° C. for 5 days in aliquid culture medium (pH 7.0) containing PD (potato dextrose, productof Difco Co.) as the seed culture, and the resulting culture solutionwas inoculated into a fermentation culture medium, i.e., a medium (pH7.0) prepared by adding 0.1% polypeptone, 0.1% yeast extract and 10%(v/v %) tomato juice (containing salt, product of Kagome Inc.) to a PD(potato dextrose) culture medium (product of Difco Co.), and the mixturewas subjected to rotatory culturing (140 rpm) at 25° C. for 12 days.

The resulting culture solution was filtered to remove the cells, andthen the filtrate from the culture was adjusted to pH 3 using 2Nhydrochloric acid. To 1.5 liters of the filtrate was added ethyl acetatefor extraction, to obtain an ethyl acetate-extracted fraction. The ethylacetate-extracted fraction was concentrated under reduced pressure, andthe solvent was removed, after which the precipitate was dissolved in asmall amount of benzene:ethyl acetate:acetic acid (80:1:2), charged intoa silica gel column which had been previously equilibrated with the sametype of solvent, and then eluted by the same type of solvent. The activefractions were concentrated and, after the solvent was removed, thesolution was applied to a Sephadex LH-20 column chromatography which hadbeen previously equilibrated with benzene and eluted by benzene:aceticacid (40:1) to obtain fractions containing the compounds A and B,respectively.

After the fraction containing the compound A was concentrated, a singlepeak portion was collected by conducting HPLC under the conditions of adevice: Shimazu LC-5A manufactured by Shimazu Manufacturing Co., Ltd. inJapan; column: Inertsil ODS-2 φ 4.6 mm×250 mm (manufactured by GLSciences, Ltd.); developing solvent: acetonitrile-water (80:20, v/v %.),flow rate: 1.0 ml/min.; temperature: 25° C.; and determination: UV 254nm, to obtain about 40 mg of the compound A. The activities of thecompounds in the culture and in the crude fractions was determined bythe paper disk method using Botrytis cinerea.

The Rf value: Silica gel thin-layer chromatography (Keisel gel 60F₂₅₄,Merck Co.) 0.35 in a solvent system of benzene:ethyl acetate:acetic acid(80:1:2, v/v %)

Production Example 1

Synthesis of3-(1-acetoxypentyl)-7-butyl-1,5-cyclooctadiene-1,2,5,6-tetracarboxylicacid di-anhydride (Compound No. 1 of the invention) ##STR50##

11.5 mg of Compound A was dissolved in 2 ml of dichloromethane andcooled to from 0 to 5° C. 10 mg of pyridine was added to the resultingsolution. After 5 minutes, 10 mg of acetyl chloride was added thereto.Then, the solution was stirred for 15 hours at room temperature. 2 ml ofchloroform and 2 ml of water were added to the solution, and the organiclayer was extracted out. The organic layer was washed with 2 ml of 1-Nhydrochloric acid and 2 ml of aqueous, saturated sodiumhydrogencarbonate solution in that order, and then dried with anhydroussodium sulfate. The solvent was removed through distillation underreduced pressure to obtain 11 mg of the intended product as oil.

Production Example 2

Synthesis of7-butyl-3-(1-methanesulfonyloxypentyl)-1,5-cyclooctadiene-1,2,5,6-tetracarboxylicacid di-anhydride (Compound No. 2 of the invention) ##STR51##

9 mg of Compound A was dissolved in 1 ml of dichloromethane and cooledto from 0 to 5° C. 4 mg of triethylamine was added to the resultingsolution, and then 5 mg of methane sulfonyl chloride was added thereto.Then, the solution was stirred for 15 hours at room temperature. 2 ml ofchloroform and 2 ml of water were added to the solution, and the organiclayer was extracted out. The organic layer was washed with 1 ml of 1-Nhydrochloric acid and 1 ml of aqueous, saturated sodiumhydrogencarbonate solution in that order, and then dried with anhydroussodium sulfate. The solvent was removed through distillation underreduced pressure, and 10 mg of a crude product was obtained. Thusobtained crude product was purified through silica gel columnchromatography (using an eluent of chloroform) to obtain 7 mg of theintended product as oil.

In the same manner as in Production Examples 1 and 2, Compound No. 3 toCompound No. 5 of the invention were synthesized. ##STR52## ProductionExample 3

Synthesis of7-butyl-3-(1-fluoropentyl)-1,5-cyclooctadiene-1,2,5,6-tetracarboxylicacid di-anhydride (Compound No. 6 of the invention) ##STR53##

0.034 ml (0.257 mmol) of DAST was dropwise added to 1 ml of a solutionof 20 mg (0,051 mmol) of Compound A in dry dichloromethane at -78° C.under the atmosphere of nitrogen. The solution was cooled to 0° C. overa period of 1 hour, while stirring, and 0.2 ml of methanol was addedthereto. The solution was extracted with 1 ml of dichloromethane andthen washed with water. The organic layer was dried with anhydrousmagnesium sulfate and then filtered. The resulting filtrate wasconcentrated under reduced pressure to obtain a crude product. Thusobtained crude product was purified through partitioning thin-layerchromatography (using an eluent of benzene/acetic acid=40:1) to obtain 7mg of the intended product as oil.

Production Example 4

Synthesis of7-butyl-3-(1-chloropentyl)-1,5-cyclooctadiene-1,2,5,6-tetracarboxylicacid di-anhydride (Compound No. 7 of the invention) ##STR54##

15 mg (0.038 mmol) of Compound A and 210 mg (0.80 mmol) oftriphenylphosphine were dissolved in 20 ml of dry carbon tetrachlorideand heated under reflux for 2 hours. The solution was cooled to roomtemperature and then washed with aqueous, saturated sodiumhydrogencarbonate solution.

The organic layer was dried with anhydrous sodium sulfate, and thesolvent was removed therefrom through distillation under reducedpressure. The resulting residue was passed two times through a short,silica gel column (using an eluent of diethyl ether). The thus obtainedcrude product was then purified through high-performance liquidchromatography (column: Inertsil ODS-2, eluent: acetonitrile/water=4:1)to obtain 10.6 mg of the intended product as oil.

Production Example 5

Synthesis of7-butyl-3-(1-pentenyl)-1,5-cyclooctadiene-1,2,5,6-tetracarboxylic aciddi-anhydride (Compound No. 8 of the invention) ##STR55##

50 mg (0.44 mmol) of t-BuOK was added all at a time to 10 ml of asolution of 17.4 mg (0.045 mmol) of Compound No. 7 in tetrahydrofuran at0° C., and then gradually heated up to room temperature. After 2 hours,200 mg (5.0 mmol) of sodium hydroxide and 5 ml of methanol were addedthereto and stirred for 30 minutes at room temperature. After thereaction, the solvent was removed through distillation under reducedpressure, and the resulting residue was made acidic by addinghydrochloric acid thereto, and then extracted with 20 ml of ethylacetate. The resulting extract was dried with anhydrous sodium sulfate,and the solvent was removed therefrom through distillation under reducedpressure. The residue was then purified through high-performance liquidchromatography (column: Inertsil ODS-2, eluent: acetonitrile/water=4:1)to obtain 4 mg of the intended product as oil.

Production Example 6

Synthesis of7-butyl-3-pentylidene-1,5-cyclooctadiene-1,2,5,6-tetracarboxylic aciddi-anhydride (Compound No. 9 of the invention) ##STR56##

One drop of diazabicycloundecene (DBU) was added to 5 ml of a solutionof 38.6 mg (0.95 mmol) of Compound No. 8 in benzene, and heated underreflux for 2 hours. After the solution was cooled to room temperature,200 mg (5.0 mmol) of sodium hydroxide and 5 ml of methanol were addedthereto and stirred for 30 minutes. The solvent was removed throughdistillation under reduced pressure, and the residue was made acidic byadding hydrochloric acid thereto, and then extracted with 20 ml of ethylacetate. The extract was dried with anhydrous sodium sulfate, and thesolvent was removed therefrom through distillation under reducedpressure. The residue was then purified through high-performance liquidchromatography (column: Inertsil-2, eluent: acetonitrile/water=4:1) toobtain 20 mg of the intended product as oil.

Production Example 7

Synthesis of7-butyl-3-pentanoyl-1,5-cyclooctadiene-1,2,5,6-tetracarboxylic aciddi-anhydride (Compound No. 10 of the invention) ##STR57##

7 mg of Compound A was dissolved in 3 ml of dichloromethane, and 1 mg ofsodium acetate was added thereto. Next, 8 mg of pyridiniumchlorochromate (PCC) was added to the resulting solution at roomtemperature and then stirred for 2 hours. 2 ml of diethyl ether wasadded to this solution, and the insoluble solids were removed throughfiltration with Celite. The solvent was removed through distillationunder reduced pressure, and 7 mg of a crude product was obtained. Thusobtained crude product was purified through silica gel columnchromatography (eluent: diethyl ether/dichloromethane=1:1) to obtain 4mg of the intended product as a white crystal.

melting point: from 203.0° to 204.0° C.

Production Example 8

Synthesis of7-butyl-3-(2-butyl-1,3-dioxolane-2-yl)-1,5-cyclooctadiene-1,2,5,6-tetracarboxylicacid di-anhydride (Compound No. 11 of the invention) ##STR58##

50 mg (0.81 mmol) of ethylene glycol and 5 mg (0.026 mmol) ofp-toluenesulfonic acid were added to 30 ml of a solution of 30 mg (0.077mmol) of Compound No. 10 in toluene, and heated under reflux for 15hours while de-watering with Dean-Stark. The solvent was removed fromthe reaction mixture through distillation under reduced pressure, and acrude product was obtained. Thus obtained crude product was purifiedthrough high-performance liquid chromatography (column: Inertsil ODS-2,eluent: acetonitrile/water=4:1) to obtain 9 mg of the intended productas oil.

Production Example 9

Synthesis of7-butyl-3-(1-(tetrahydropyran-2-yloxy)pentyl)-1,5-cyclooctadiene-1,2,5,6-tetracarboxylicacid di-anhydride (Compound No. 12 (epimer 1) of the invention andCompound No. 13 (epimer 2) of the invention) ##STR59##

20 mg (0.051 mmol) of Compound A was dissolved in 0.5 ml ofdichloromethane, 2 mg (0.012 mmol) of p-toluenesulfonic acid was addedthereto, and 0.01 ml (0.11 mmol) of dihydropyran was added thereto at 0°C. Then, the solution was stirred for 30 minutes. One ml of aqueous,saturated sodium hydrogencarbonate solution was added to the solution,which was then extracted two times with 5 ml of dichloromethane. Theorganic layer was dried with anhydrous magnesium sulfate, and filtered,and the resulting filtrate was concentrated under reduced pressure toobtain a crude product. Thus obtained crude product was purified throughhigh-performance liquid chromatography (column: Inertsil ODS-2, eluent:acetonitrile/water=4:1) to obtain 6 mg of epimer 1 (polar, oilysubstance) and 5 mg of epimer 2 (low-polar, crystal).

Production Example 10

Synthesis of7-butyl-3-(1-hydroxypentyl)-1,5-cyclooctadiene-1,2,5,6-tetracarboxylicacid N,N'-dimethyldiimide (Compound No. 14 of the invention) ##STR60##

8 mg (0.064 mmol) of aqueous, 25-% methylamine solution was added to 0.5ml of a solution of 10 mg (0.026 mmol) of Compound A in acetic acid,stirred for 15 hours at room temperature, and then heated under refluxfor 8 hours. The solvent was removed through distillation under reducedpressure to obtain a crude product. Thus obtained crude product waspurified through silica gel column chromatography (eluent: hexane/ethylacetate=1:1) to obtain 10 mg of the intended product as oil.

In the same manner as in Procution Example 10, Compound No. 15 toCompound No. 17 of the present invention were synthesized. ##STR61##Production Example 11

Synthesis of Compound No. 18 of the invention ##STR62##

20 ml of a solution of 2.2 g of1,4-dimethoxy-2,3-bis(chloromethyl)benzene in tetrahydrofuran (THF) wasdropwise added to a suspension that had been prepared by suspending 5.4g of 35-% potassium hydride in 50 ml of THF, at from 0° to 5° C. Afterthe solution was stirred for 10 minutes, 20 ml of a solution of 1.8 g of4,7-dimethoxyindan-2-one in THF was dropwise added thereto at from 0° to5° C. Next, the solution was stirred for 4 hours at room temperature.The resulting solution was poured into water with ice and thenconcentrated under reduced pressure. The solution was made neutral byadding 2-N hydrochloric acid thereto, and then extracted two times with80 ml of chloroform. The resulting organic layer was dried withanhydrous magnesium sulfate, and the solvent was removed therefromthrough distillation under reduced pressure to obtain 6.4 g of a crudeproduct. Thus obtained crude product was purified through silica gelcolumn chromatography, and 2.4 g of a crude crystalline product wasobtained. Thus obtained crude crystalline product was washed withdiethyl ether, filtered and dried to obtain 1.6 g of the intendedproduct.

melting point: from 232.0° to 235.0° C.

Production Example 12

Synthesis of Compound No. 19 of the invention ##STR63##

2 g of Compound No. 18 was dissolved in 80 ml of dichloromethane, and 4g of sodium hydrogencarbonate and 1.34 g of m-chloro-perbenzoic acid(m-CPBA) were added to the resulting solution in that order at roomtemperature, and then stirred for 15 hours. The solution was extractedwith 80 ml of chloroform and 80 ml of water added thereto. The resultingorganic layer was washed with an aqueous sodium hydrogencarbonatesolution, and then dried with anhydrous magnesium sulfate. The solventwas removed through distillation under reduced pressure to obtain 2.1 gof a crude, crystalline product. Thus obtained crude, crystallineproduct was washed with 10 ml of diethyl ether, filtered and dried toobtain 1.6 g of the intended product.

melting point: from 184.0° to 186.0° C.

Production Example 13

Synthesis of Compound No. 20 of the invention ##STR64##

100 mg of Compound No. 19 was dissolved in 20 ml of dry THF, and 1.5 mlof a solution of 1.9M of butyl magnesium chloride in THF was dropwiseadded to the resulting solution at room temperature and then stirred for10 minutes. The solution was poured into water, and 2-N hydrochloricacid was added thereto. The solution was then extracted with 50 ml ofdiethyl ether. The resulting organic layer was dried with anhydrousmagnesium sulfate, and the solvent was removed therefrom throughdistillation under reduced pressure to obtain 110 mg of the intendedproduct as oil.

Production Example 14

Synthesis of Compound No. 21 of the invention ##STR65##

100 mg of Compound No. 20 was dissolved in 20 ml of dry THF. 10 mg oflithium aluminium hydride (LiAlH4) was added to the resulting solutionat from 0° to 5° C. and then stirred at room temperature for 1 hour.Water and 2-N hydrochloric acid were added to the solution, which wasthen extracted with 40 ml of diethyl ether. The resulting organic layerwas dried with anhydrous magnesium sulfate, and the solvent was removedtherefrom through distillation under reduced pressure to obtain 90 mg ofa crude, crystalline product. Thus obtained crude, crystalline productwas washed with 2 ml of diethyl ether, filtered and dried to obtain 80mg of the intended product.

melting point: from 217.0° to 219.0° C.

Production Example 15

Synthesis of Compound No. 22 of the invention ##STR66##

50 mg of Compound No. 21 was dissolved in 5 ml of dichloromethane, and100 mg of manganese dioxide was added thereto at room temperature andthen stirred for 15 hours. The solution was filtered, and the solventwas removed from the resulting filtrate through distillation underreduced pressure to obtain 47 mg of the intended product as a crystal.

melting point: from 185.0° to 188.0° C.

Production Example 16

Synthesis of Compound No. 23 of the invention ##STR67##

50 mg of Compound No. 21 of was dissolved in 5 ml of dichloromethane. 28mg of pyridine and 24 mg of benzoyl chloride were dropwise added to theresulting solution at 0° C., and then the solution was stirred at roomtemperature for 1 hour. Water was added to the solution and then,extracted with 20 ml of ethyl acetate added thereto. The resultingorganic layer was washed with 2-N hydrochloric acid and an aqueoussodium hydrogencarbonate solution in that order, and then dried withanhydrous magnesium sulfate. The solvent was removed throughdistillation under reduced pressure to obtain 62 mg of a crude product.Thus obtained crude product was partitioned through silica gelthin-layer chromatography to obtain 40 mg of the intended product asoil.

Production Example 17

Synthesis of Compound No. 24 of the invention ##STR68##

0.5 ml of a solution of 37 mg of dimethylsulfoxide dissolved indichloromethane was dropwise added to 0.5 ml of dichloromethanecontaining 0.03 ml of oxalyl chloride as dissolved therein, at -78° C.,and then stirred for 5 minutes. Next, 3 ml of a solution of 45 mg ofCompound No. 23 as dissolved in dichloromethane was dropwise addedthereto at -78° C. and then stirred for 1 hour. Next, 0.2 ml oftriethylamine was dropwise added thereto at -40° C., and then stirred at0° C. for 20 minutes. The resulting solution was extracted with 2 ml ofdichloromethane and 2 ml of water added thereto, and the resultingorganic layer was washed with 1-N hydrochloric acid and then dried withanhydrous magnesium sulfate. The solvent was removed throughdistillation under reduced pressure, and 44 mg of the intended productwas obtained as a crystal.

melting point: from 178.0° to 180.0° C.

Production Example 18

Synthesis of Compound No. 25 of the invention ##STR69##

45 mg of Compound No. 21 was dissolved in 10 ml of dichloromethane. 160mg of triethylamine and 100 mg of chloromethyl methyl ether was addedthereto in that order at room temperature, and then stirred for 2 hours.Next, 160 mg of triethylamine and 100 mg of chloromethyl methyl etherwere further added thereto, and stirred for 1 hour. This operation wasrepeated two times, and thereafter the solution was left as it was for15 hours. Water was added to the solution, which was then extracted with50 ml of chloroform. The resulting organic layer was washed with 1-Nhydrochloric acid and then dried with anhydrous magnesium sulfate. Thesolvent was removed through distillation under reduced pressure, and 50mg of a crude product was obtained. Thus obtained crude product waspurified through silica gel column chromatography to obtain 35 mg of theintended product as a crystal.

melting point: from 120.0° to 125.0° C.

Production Example 19

Synthesis of Compound No. 26 of the invention ##STR70##

35 mg of Compound No. 25 was dissolved in 10 ml of dichloromethane. 40mg of sodium acetate and 70 mg of pyridinium chlorocromate (PCC) wereadded to the solution in that order, and then stirred for 15 hours atroom temperature. The solution was extracted with water and diethylether added thereto. The resulting organic layer was washed with waterand then dried with anhydrous magnesium sulfate. The solvent was removedthrough distillation under reduced pressure, and 35 mg of a crudeproduct was obtained. Thus obtained crude product was purified throughsilica gel column chromatography to obtain 31 mg of the intended productas a crystal.

melting point: from 130.0° to 133.0° C.

The physical properties of the compounds of the present invention areshown in Table 6.

                  TABLE 6                                                         ______________________________________                                                 Physical                                                                      property                                                                            .sup.1 H-NMR (δ, CDCl.sub.3 ; TMS)                       ______________________________________                                                       MS                                                             Compound No. 1                                                                           oil     0.90-0.99(m, 6H), 1.30-1.48(m, 8H),                        of the             1.59-1.72(m, 2H), 1.74-1.89(m, 2H)                         present            2.02(s, 3H), 2.86-3.05(m, 4H),                             invention          3.10-3.20(m, 2H), 5.20-5.28(m, 1H)                         Compound No. 2                                                                           oil     0.90-1.00(m, 6H), 1.30-1.98(m, 12H),                       of the             2.90-3.14(m, 5H), 3.01(s, 3H),                             present            3.18-3.28(m, 1H), 4.99-5.03(m, 1H)                         invention                                                                     Compound No. 3                                                                           oil     0.02(s, 9H), 0.93-0.98(m, 6H),                             of the             1.25-1.64(m, 12H), 2.85-3.05(m, 5H),                       present            3.26(t, J=13.2Hz, 1H), 4.00(m, 1H)                         invention          MS; 462(M.sup.+), 447, 405, 376, 361,                                         333, 304, 160                                              Compound No. 4                                                                           oil     0.93-0.95(m, 6H), 1.26-2.00(m, 12H),                       of the             2.56-3.14(m, 6H),                                          present            4.99(dt, J=7.5Hz 7.0Hz, 1H)                                invention          7.13-7.36(m, 10H)                                                             MS(FAB); 623(M+1), 251                                     Compound No. 5                                                                           oil     0.88-0.99(m, 6H), 1.26-1.75(m, 12H),                       of the             2.93-3.17(m, 6H), 5.12(m, 1H),                             prsent             6.67(bs, 1H), 7.25.7.41(m, 4H)                             invention          MS(FAB); 544(M+1), 373, 355, 172                           Compound No. 6                                                                           oil     0.85-1.00(m, 6H), 1.20-1.89(m, 12H),                       of the             2.95-3.10(m, 4H), 3.20-3.31(m, 1H),                        present            3.35-3.42(m, 1H),                                          invention          4.70(ddt, J=47.9Hz 8.4Hz 7.0Hz, 1H)                                           MS(FAB); 393(M+1), 3.72                                    Compound No. 6                                                                           oil     0.85-100(m, 6H), 1.20-1.89(m, 12H),                        of the             2.95-3.10(m, 4H), 3.20-3.31(m, 1H),                        present            3.35-3.42(m, 1H),                                          invention          4.70(ddt, J=47.9Hz 8.4Hz 7.0Hz, 1H)                                           MS(FAB); 393(M+1), 372                                     Compound No. 7                                                                           oil     0.91-1.88(m, 18H), 2.96-3.05(m, 3H),                       of the             3.22(t, J=12.7Hz, 1H),                                     present            3.49(t, J=12.9Hz, 1H),                                     invention          4.16-4.20(m, 1H)                                                              MS(FAB); 409(M+1), 373, 307                                Compound No. 8                                                                           oil     0.85-1.00(m, 6H), 1.25-2.04(m, 10H),                       of the             2.99-3.09(m, 5H), 3.59(m, 1H),                             present            5.38(ddt, J=15.4Hz 7.5Hz 1.0Hz, 1H),                       invention          5.76(ddt, J=15.4Hz 7.7Hz 1.0Hz, 1H)                                           MS(FAB); 377(M+1), 307, 279                                Compound No. 9                                                                           oil     0.89-1.85(m, 16H), 2.45(m, 1H),                            of the             2.53(m, H), 3.01-3.10(m, 3H),                              present            3.68(d, J=14.8Hz, 12H),                                    invention          3.94(d, J=14.8Hz, 1H),                                                        7.33(t, J=6.6Hz, 1H)                                                          MS; 372                                                    Compound No. 10                                                                          white   m.p. 203.0-204.0° C.                                           crystal                                                            Compound No. 11                                                                          oil     0.98-1.00(m, 6H), 1.20-1.86(m, 12H),                       of the             2.96-3.04(m, 3H), 3.10-3.25(m, 2H),                        present            3.47(dd, J=12.8Hz, 6.3Hz, 1H),                             invention          3.88-3.96(m, 2H), 3.94-4.06(m, 2H)                                            MS(FAB); 433(M+1)                                          Compound No. 12                                                                          oil     0.91-1.00(m, 6H), 1.25-1.58(m, 18H),                       of the             2.88-3.02(m, 3H), 3.03-3.12(m, 2H),                        present            3.25(m, 1H), 3.43-3.49(m, 1H),                             invention          3.86-3.94(m, 2H), 4.32-4.36(m, 1H)                                            MS(FAB); 475(M+1), 473                                     Compound No. 13                                                                          white   m.p. 168-170.0° C.                                             crystal                                                            Compound No. 14                                                                          oil     0.88-0.99(m, 6H), 1.24-1.88(m, 13H),                       of the             2.80-3.00(m, 5H), 2.97(s, 6H),                             present            3.08-3.13(m, 1H), 3.90-3.94(m, 1H),                        invention          3.94(d, J=14.8Hz, 1H),                                                        MS(FAB); 417(M+1)                                          Compound No. 15                                                                          oil     0.82-1.00(m, 6H), 1.20-1.80(m, 12H),                       of the             2.10(bs, 1H), 2.79-2.89(m, 3H),                            present            2.90-3.00(m, 2H), 3.03-3.12(m, 1H),                        invention          3.89-3.92(m, 1H), 7.97(bs, 1H),                                               8.10(bs, 1H)                                                                  MS(FAB); 389(M+1)                                          Compound No. 16                                                                          oil     0.90-1.00(m, 6H), 1.20-1.80(m, 13H),                       of the             2.80-2.99(m, 5H), 3.06-3.13(m, 1H),                        present            3.90-3.94(m, 1H), 4.52-4.68(m, 4H),                        invention          7.25-7.39(m, 10H)                                                             MS(FAB); 569(M+1)                                          Compound No. 17                                                                          oil     0.90-1.00(m, 6H), 1.26-1.43(m, 6H),                        of the             1.53-1.65(m, 3H), 1.75(m, 1H),                             present            2.73(t, J=7.6Hz, 1H),                                      invention          2.85-3.00(m, 4H),                                                             3.22(t, J=13.4Hz, 1H),                                                        3.93(dd, J=12.9Hz 5.4Hz, 1H),                                                 7.91-8.09(bs, 2H)                                                             MS(FAB); 387(M+1)                                          Compound No. 18                                                                          white   m.p. 232.0-235.0° C.                                           crystal                                                            Compound No. 19                                                                          white   m.p. 184.0-186.0° C.                                           crystal                                                            Compound No. 20                                                                          oil     0.78-1.08(m, 3H), 1.23-1.75(m, 6H),                        of the             1.88-2.20(m, 3H), 3.45-3.80(m, 3H),                        present            3.58(s, 3H), 3.62(s, 3H),                                  invention          3.67(s, 3H), 3.69(s, 3H),                                                     3.95-4.04(m, 1H), 6.38-6.54(m, 4H),                        Compound No. 21                                                                          white   m.p. 217.0-219.0° C.                                           crystal                                                            Compound No. 22                                                                          white   m.p. 185.0-188.0° C.                                           crystal                                                            Compound No. 23                                                                          oil     0.78-0.85(m, 3H), 1.10-1.80(m, 7H),                        of the             2.93-3.02(m, 3H), 3.38-3.50(m, 2H),                        present            3.60(s, 3H), 3.68(s, 6H),                                  invention          3.70(s, 3H), 3.95-4.04(m, 1H),                                                4.30-4.40(m, 1H), 6.04-6.18(bs, 2H),                                          6.47(s, 2H), 6.50-6.65(m, 2H),                                                7.40-7.50(m, 2H), 7.54-7.63(m, 1H),                                           8.09-8.20(m, 2H)                                           Compound No. 24                                                                          white   m.p. 178.0-180.0° C.                                           crystal                                                            Compound No. 25                                                                          white   m.p. 120.0-125.0° C.                                           crystal                                                            Compound No. 26                                                                          white   m.p. 130.0-133.0° C.                                           crystal                                                            ______________________________________                                    

Formulation examples of fungicides comprising the compound of thepresent invention as the active ingredient are mentioned hereinunder,which, however, are not limitative. In the following formulationexamples, "parts" are by weight.

Formulation Example 1: Emulsifiable concentrates

    ______________________________________                                        Compound of the invention                                                                        20 parts                                                   Xylene             55 parts                                                   N,N-dimethylformamide                                                                            20 parts                                                   Solpol 2680 (trade name,                                                                          5 parts                                                   a mixture of a nonionic                                                       surface-active agent and                                                      an anionic-surface active                                                     agent manufactured by                                                         Toho Chemical Co., Ltd.)                                                      ______________________________________                                    

The above-mentioned components are homogeneously mixed together to forman emulsifiable concentrate. Upon use, the emulsifiable concentrate isdiluted from 50 to 20000 times and applied in an amount of from 5 g/hato 50 kg/ha in terms of the active ingredient.

Formulation Example 2: Wettable powders

    ______________________________________                                        Compound of the invention                                                                        25 parts                                                   Zeeklite PFP (trade name,                                                                        66 parts                                                   a mixture of kaolinite and                                                    sericite manufactured by                                                      Zeeklite Mining Industries                                                    Co., Ltd.)                                                                    Solpol 5039 (trade name,                                                                          4 parts                                                   an anionic-surface active                                                     agent manufactured by                                                         Toho Chemical Co., Ltd.)                                                      Carplex #80 (trade name,                                                                          3 parts                                                   white carbon manufactured                                                     by Shionogi Pharmaceutical                                                    Co., Ltd.)                                                                    Calcium lignin sulfonate                                                                          2 parts                                                   ______________________________________                                    

The above-mentioned components are homogeneously mixed together andground to form a wettable powder. Upon use, the wettable powder isdiluted with from 50 to 20000 times and applied in an amount of from 5g/ha to 50 kg/ha in terms of the active ingredient.

Formulation Example 3: Oil solutions

    ______________________________________                                        Compound of the invention                                                                        10 parts                                                   Methyl cellosolve  90 parts                                                   ______________________________________                                    

The above-mentioned components are homogeneouly mixed together to forman oil solution. Upon use, the oil solution is applied in an amount offrom 5 g/ha to 50 kg/ha in terms of the active ingredient.

Formulation Example 4: Dusts

    ______________________________________                                        Compound of the invention                                                                            3 parts                                                Carplex #80 (trade name,                                                                             0.5 parts                                              white carbon manufactured                                                     by Shionogi Pharmaceutical                                                    Co., Ltd.)                                                                    Clay                   95 parts                                               Di-isopropyl phosphate 1.5 parts                                              ______________________________________                                    

The above-mentioned components are homogeneously mixed together andground to form a dust. Upon use, the dust is applied in an amount offrom 5 g/ha to 50 kg/ha in terms of the active ingredient.

Formulation Example 5: Granules

    ______________________________________                                        Compound of the invention                                                                             5 parts                                               Bentonite              54 parts                                               Talc                   40 parts                                               Calcium ligninsulfonate                                                                               1 part                                                ______________________________________                                    

The above-mentioned components are mixed homogeneously together andground, incorporated with a small amount of water and mixed togetherwith stirring. The resulting mixture is granulated by means ofextrusion-granulator and dried to form granules. Upon use, the granulesare applied in an amount of from 5 g/ha to 50 kg/ha in terms of theactive ingredient.

Formulation Example 6: Flowables

    ______________________________________                                        Compound of the invention                                                                             25 parts                                              Solpol 3358 (trade name,                                                                              10 parts                                              a nonionic surface-active agent                                               manufactured by Toho Chemical                                                 Co., Ltd.)                                                                    Runox 1000C (trade name,                                                                              0.5 parts                                             an anionic surface-active agent                                               manufactured by Toho Chemical                                                 Co., Ltd.)                                                                    1% aqueous solution Xanthan                                                                           20 parts                                              gum (high molecular compound)                                                 Water                   44.5 parts                                            ______________________________________                                    

The above-mentioned components except the active ingredient arehomogeneously melted, and then the compound of the invention is addedthereto and well stirred. The resulting mixture is wet-ground in a sandmill to obtain a flowable. Upon use, the flowable is diluted from 50 to20000 times and applied in an amount of from 5 g/ha to 50 kg/ha in termsof the active ingredient.

Next, formulation examples of medicines comprising the novel compound ofthe present invention as the active ingredient are mentionedhereinunder, which, however, are not limitative.

Formulation Example 7: Liquid liniment

    ______________________________________                                        Compound of the invention                                                                         3 parts                                                   Diethanolamine     10 parts                                                   Ethanol            87 parts                                                   ______________________________________                                    

Diethanolamine is added to a small amount of ethanol and stirred toprepare a uniform solution. The compound of the invention is added tothe resulting solution and dissolved therein by stirring it. Next, theremaining ethanol is added thereto to obtain a liquid liniment.

Formulation Example 8: Ointment

    ______________________________________                                        Compound of the invention                                                                             1 part                                                Diethanolamine          3 parts                                               White petrolatum       86 parts                                               Stearic acid           10 parts                                               ______________________________________                                    

White petrolatum and stearic acid are heated and melted, anddiethanolamine is added thereto to prepare a uniform solution. Thecompound of the invention is added to the solution and dissolved thereinby stirring it. The resulting solution is solidified at room temperatureto obtain an ointment.

Formulation Example 9: Tablet

    ______________________________________                                        Compound of the invention                                                                          10        g                                              Lactose              20        g                                              Starch               4         g                                              Starch (for paste)   1         g                                              Magnesium stearate   100       mg                                             Calcium carboxymethyl cellulose                                                                    7         g                                              Total                42.1      g                                              ______________________________________                                    

The above-mentioned components are mixed in an ordinary manner, and thenformed into sugar-coated tablets each containing 50 mg/tablet of theactive ingredient.

Formulation Example 10: Capsule

    ______________________________________                                        Compound of the invention                                                                        10 g                                                       Lactose            20 g                                                       Microcrystalline cellulose                                                                       10 g                                                       Magnesium stearate  1 g                                                       Total              41 g                                                       ______________________________________                                    

The above-mentioned components are mixed in an ordinary manner, and thenencapsulated into gelatin capsules. The capsules thus formed contain 50mg/capsule of the active ingredient.

Formulation Example 11: Soft capsules

    ______________________________________                                        Compound of the invention                                                                        10 g                                                       Corn oil           35 g                                                       Total              45 g                                                       ______________________________________                                    

The above-mentioned components are mixed, and then formed into softcapsules in an ordinary manner.

Formulation Example 12: Ointment

    ______________________________________                                        Compound of the invention                                                                            1.0 g                                                  Olive oil              20 g                                                   White petrolatum       79 g                                                   Total                  100 g                                                  ______________________________________                                    

The above-mentioned components are mixed in an ordinary manner toprepare a 1-% ointment.

Formulation Example 13: Aerosol suspension

    ______________________________________                                        (A)                                                                           Compound of the invention                                                                        0.25%                                                      Isopropyl myristate                                                                              0.10%                                                      Ethanol            26.40%                                                     (B)                                                                           60 to % 40 mixture of                                                                            73.25%                                                     1,2-dichlorotetra-                                                            fluoroethane and 1-chloro-                                                    pentafluoroethane                                                             ______________________________________                                    

The components of (A) are mixed, and the resulting composition (A) ischarged into a container provided with a valve. The propellant (B) isjetted into the container through the valve nozzle, at 20° C., up to agauge pressure of approximately from 2.46 to 2.81 mg/cm², to prepare anaerosol suspension.

Next, the effectiveness of the compounds of the present invention isdemonstrated in the following Test Examples, which, however, are notlimitative.

Test Example 1

Test for the fungicidal activity of the compounds of the inventionagainst Botrytis cinerea:

Inhibition of Growth of Hyphae

One ml of a chemical liquid to be tested, having a concentration of 10times of a pre-determined concentration, was put into a laboratory dish,and 9 ml of a potato-sucrose-agar (PSA) medium that had been sterilizedand melted was added thereto and solidified to give a plate medium.Cells of Botrytis cinerea were grown on a PSA medium, and a disc wasstamped out from the medium, using a cork borer having a diameter of 4mm, and put on the previously-prepared, plate PSA medium containing thechemical. The cells were thus incubated thereon at 25° C. for 3 days,and the diameters of the mycelia thus grown were measured. From thedata, calculated was the percentage of inhibition of the growth ofhyphae according to the following equation.

    Percentage of inhibition of Growth of Hyphae (%)= (diameter in control area with no chemical added)-(diameter in test area with chemical added)!/(diameter in control area with no chemical added)×100

Inhibition of Germination of Spores

Yeast extract and sucrose were added to a suspension of spores ofBotrytis cinerea at a final concentration of 3% and 1%, respectively.This was mixed with a chemical liquid to be tested, and the resultingmixture was dropped onto a glass slide. This was incubated at 25° C. andat a high humidity for 20 hours, and then observed with a microscope.The number of the non-germinated spores/50 spores was counted.

    Percentage of Inhibition of Germination of Spores= (non-germinated spores)/50!×100

The results are shown in Table 7.

                  TABLE 7                                                         ______________________________________                                                              Inhibition of                                                                           Inhibition of                                 Compound of                                                                              Concent-   Growth of Germination                                   the Invention                                                                            tion (ppm) Hyphae (%)                                                                              of Spores (%)                                 ______________________________________                                        No. 1      100        100       100                                           No. 2      100         88       100                                           No. 3      100        100       100                                           No. 5      100         73                                                     No. 6      100        100       100                                           No. 7      100         80                                                     No. 8      100        100       100                                           No. 9      100        100       100                                            No. 10    100        100        76                                            No. 11    100        100       100                                            No. 12    100        100       100                                            No. 13    100         81                                                      No. 15    100         21                                                      No. 17    100         61                                                     ______________________________________                                    

Test Example 2

Test for disease controlling activity against gray mold:

A chemical liquid as prepared by diluting an emulsifiable concentratecomprising Compound No. 6 of the invention with water to have aconcentration of 500 ppm was sprayed through a spray gun over one ortwo-leaves stage, cucumber seedlings (variety: Sagami-hanjiro) that hadgrown in pots having a diameter of 7 cm, the amount of the liquidsprayed being 20 ml/pot. On the next day, the leaves were cut out of theseedlings and put onto paper as wetted with water in a vat. A disc(diameter: 4 mm) of the mycelial plexa of Botrytis cinerea that had beenincubated in a PSA medium was inoculated on the leaves. After theinoculation, the vat was covered with a vinyl cover and put in athermostat at 18° C. for 5 days. The diameters of the disease lesionformed were measured. The protective value was obtained according to thefollowing equation.

    Extermination value= (diameter (mm) of lesion in non-treated plot)-(diameter (mm) of lesion in treated plot)!/(diameter (m m) of lesion in non-treated plot)×100

The protective value of Compound No. 6 tested herein was 100.

Test Example 3

Test for the anti-thrombocytoagglutination activity of the compounds ofthe invention in rats:

Test Method

Using a syringe containing therein 1 part by volume of 3.8-% sodiumcitrate, 9 parts by volume of blood was collected from a male, Wisterrat (body weight: 200 to 300 g) through its abdominal aorta. The bloodwas centrifuged at 200×g for 7 minutes at room temperature to prepare aplatelet-rich plasma (PRP) sample. Next, the residue was furthercentrifuged at 2,000×g for 10 minutes to prepare a platelet-poor plasma(PPP) sample.

PRP and PPP samples were diluted to have a concentration of 300,000cells/mm³, and these dilutions were used herein. Each sample was putinto an agglutination cell. The range for the measurement of thetransmittance through the cell was settled at 0% for PRP and at 100% forPPP. A chemical to be tested was dissolved in 100-% dimethylsulfoxide(DMSO), and the resulting chemical solution was added to the cellcontaining PRP at a final DMSO concentration of 0.25%. The samples werethen incubated at 37° C. and at 900 rpm for 2 minutes. After theincubation, an agglutinant was added to these, and the agglutinationcurves were recorded. The anti-agglutination activity of the chemicaltested was represented by the concentration thereof, at which theagglutination was inhibited by 50% of the control, IC₅₀ (μM). Theconcentrations of the agglutinants ADP, collagen and U46619 employedherein were their minimum concentrations at which they induce thehighest agglutination (ADP: 5 to 10 μM; collagen: 2.5 to 10 μg/ml;U46619: 0.5 to 1 μM). For the measurement of thethrombocytoagglutination, herein employed was NBS HEMA TRACER 601.

The results are shown in Table 8.

                  TABLE 8                                                         ______________________________________                                                   IC.sub.50 (μM)                                                             ADP      Collagen U46619                                           ______________________________________                                        Compound No. 6                                                                              9         158      905                                          Compound No. 9                                                                             172        474                                                   Compound No. 10                                                                            67         105      632                                          Compound No. 12                                                                            84         194      239                                          ______________________________________                                         U46619                                                                        ##STR71##                                                                

INDUSTRIAL APPLICABILITY

As has been described hereinabove, the cyclooctadiene derivatives of thepresent invention have excellent bactericidal activity and antimoldactivity and also have anti-thrombocytoagglutination activity, and aretherefore useful as bactericides, antimolds and antithrombocytic agents.

We claim:
 1. A cyclooctadiene derivative of the formula (1): ##STR72##wherein A¹, A², A³ and A⁴ each independently represent COOR⁵ (where R⁵represents a hydrogen atom, a C₁ -C₁₀ alkyl group, a C₂ -C₁₀ alkenylgroup, a C₂ -C₁₀ alkynyl group, a phenyl group (the phenyl group may beoptionally substituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or a nitrogroup), or a C₇ -C₁₂ aralkyl group (the aralkyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group)), orCONR⁶ R⁷ (where R⁶ and R⁷ each independently represent a hydrogen atom,a C₁ -C₁₀ alkyl group or a phenyl group (the phenyl group may beoptionally substituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or a nitrogroup)), or A¹ and A², and/or A³ and A⁴ may be combined together torepresent group(s) of: ##STR73## in which X represents an oxygen atom orNR⁸ {where R⁸ represents a hydrogen atom, a C₁ -C₁₀ alkyl group, aphenyl group (the phenyl group may be optionally substituted by ahalogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group), or a C₇ -C₁₂ aralkylgroup (the aralkyl group may be optionally substituted by a halogenatom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxygroup, a cyano group and/or a nitro group)};R⁰, R¹, R², R³ and R⁴ eachindependently represent a hydrogen atom, a halogen atom, a hydroxylgroup, an optionally-substituted C₁ -C₁₀ alkyl group, anoptionally-substituted C₂ -C₁₀ alkenyl group, or anoptionally-substituted C₂ -C₁₀ alkynyl group; the substituent for theoptionally-substituted groups can be any one or more selected from thegroup consisting of a halogen atom, a C₁ -C₆ alkyl group, a C₂ -C₆alkenyl group, a C₂ -C₆ alkynyl group, a C₁ -C₆ haloalkyl group, OR⁹{where R⁹ represents a hydrogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆alkenyl group, a C₂ -C₆ alkynyl group, a C₁ -C₆ haloalkyl group, a silylgroup, a C₁ -C₄ alkylsulfonyl group, a C₇ -C₁₂ aralkyl group (thearalkyl group may be optionally substituted by a halogen atom, a C₁ -C₆alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, a cyanogroup and/or a nitro group), a phosphoryl group, a C₂ -C₁₀ alkoxyalkylgroup, or COR¹⁴ where R¹⁴ represents a C₁ -C₆ alkyl group, a phenylgroup (the phenyl group may be optionally substituted by a halogen atom,a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, acyano group and/or a nitro group), a C₁ -C₆ alkoxy group, or NR¹⁵ R¹⁶(where R¹⁵ and R¹⁶ each independently represent a hydrogen atom, a C₁-C₆ alkyl group or a phenyl group (the phenyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group)))},SR¹⁰ (where R¹⁰ represents a hydrogen atom, a C₁ -C₆ alkyl group, a C₂-C₆ alkenyl group, a C₂ -C₆ alkynyl group, a C₇ -C₁₂ aralkyl group (thearalkyl group may be optionally substituted by a halogen atom, a C₁ -C₆alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, a cyanogroup and/or a nitro group), NR¹¹ R¹² {where R¹¹ and R¹² eachindependently represent a hydrogen atom, a C₁ -C₆ alkyl group, a phenylgroup (the phenyl group may be optionally substituted by a halogen atom,a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, acyano group and/or a nitro group) or COR¹⁷ (where R¹⁷ represents a C₁-C₆ alkyl group, a phenyl group (the phenyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group) or C₁-C₆ alkoxy group)}, ═O, ═NR¹³ {where R¹³ represents a C₁ -C₆ alkylgroup, a phenyl group (the phenyl group may be optionally substituted bya halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆alkoxy group, a cyano group and/or a nitro group) or OR¹⁸ (where R¹⁸represents a hydrogen atom, a C₁ -C₆ alkyl group or COR¹⁹ (where R¹⁹represents a C₁ -C₆ alkyl group, a phenyl group (the phenyl group may beoptionally substituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or a nitrogroup) or NR²⁰ R²¹ (where R²⁰ and R²¹ each independently represent ahydrogen atom, a C₁ -C₆ alkyl group, a phenyl group (the phenyl groupmay be optionally substituted by a halogen atom, a C₁ -C₆ alkyl group, aC₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or anitro group))))}, and ##STR74## (where m is an integer of from 2 to 4);the symbol ------ represents a single or double bond, and when it is adouble bond, then R¹ and R³ each independently may represent an oxygenatom; provided that the case where all of R⁰, R¹, R², R³ and R⁴represent hydrogen atoms at the same time is excluded.
 2. Cyclooctadienederivatives as claimed in claim 1, wherein R⁰, R² and R³ eachindependently represent a hydrogen atom, a halogen atom, a hydroxylgroup or a C₁ -C₁₀ alkyl group, or R³ represents ═O.
 3. Cyclooctadienederivatives as claimed in claim 2, wherein R⁴ represents a hydrogenatom, a halogen atom or a C₁ -C₁₀ alkyl group.
 4. Cyclooctadienederivatives as claimed in claim 3, wherein A¹, A², A³ and A⁴ eachindependently represent COOR²² (where R²² represents a hydrogen atom ora C₁ -C₁₀ alkyl group), or A¹ and A², and A³ and A⁴ are combinedtogether to represent a group of: ##STR75##
 5. Cyclooctadienederivatives as claimed in claim 4, whereinR⁰, R² and R³ representhydrogen atoms; R⁴ represents --CH₂ CH₂ CH₂ CH₃ ; R¹ represents a groupof: ##STR76## or a group of: ##STR77## R²³ represents a hydrogen atom, ahalogen atom, a C₁ -C₆ alkyl group or a C₁ -C₆ alkoxy group; R²⁴represents a hydrogen atom, a halogen atom, a C₁ -C₆ alkyl group, --OR²⁷{where R²⁷ represents a hydrogen atom, C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₇ -C₁₂ aralkyl group (the aralkyl group may beoptionally substituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆haloalkyl group, a C₁ -C₆ alkoxy group, a cyano group and/or a nitrogroup), a C₂ -C₆ alkoxyalkyl group or --COR²⁸ (where R²⁸ represents a C₁-C₆ alkyl group, a phenyl group (the phenyl group may be optionallysubstituted by a halogen atom, a C₁ -C₆ alkyl group, a C₁ -C₆ haloalkylgroup, a C₁ -C₆ alkoxy group, a cyano group and/or a nitro group), a C₁-C₆ alkoxy group or NR²⁹ R³⁰ (where R²⁹ and R³⁰ each independentlyrepresent a hydrogen atom, a C₁ -C₆ alkyl group or a phenyl group (thephenyl group may be optionally substituted by a halogen atom, a C₁ -C₆alkyl group, a C₁ -C₆ haloalkyl group, a C₁ -C₆ alkoxy group, a cyanogroup and/or a nitro group)))}, or R²³ and R²⁴ are combined together torepresent ═O or a group of: ##STR78## (where m is an integer of from 2to 4); R²⁵ represents a hydrogen atom, a halogen atom or a C₁ -C₆ alkylgroup; R²⁶ represents a hydrogen atom, a halogen atom or a C₁ -C₆ alkylgroup; and the symbol ------ represents a single or double bond. 6.Compound of formula (2): ##STR79##
 7. Compound of formula (3): ##STR80##8. Compounds of formula (4): ##STR81## wherein R³¹ represents a C₁ -C₁₀alkyl group or a C₂ -C₁₀ alkenyl group.
 9. An agrohorticulturalfungicide comprising one or more of the cyclooctadiene derivatives asclaimed in claim 1 and a carrier.
 10. An antimold agent comprising oneor more of the cyclooctadiene derivatives as claimed in claim 1 and adiluent.
 11. An antithrombocytic agent comprising one or more of thecyclooctadiene derivatives as claimed in claim 1 and a diluent.